Free Trade is Fraud. There is Nothing Free About the Carbon Cost Dumped on the Atmosphere. 2022-1-30. Jorma Antero Jyrkkanen

Is Trade Free? Not in any aspect. Every movement of goods anywhere in the world has an environmental cost due to the energy consumed. That energy is used in making the infrastructure of trade, the transportation equipment, spent in the delivery and distribution.

932 MILLION TONNES(1000 KGS)=932 BILLION KGS CO2 IS PROOF FREE TRADE IS DEADLY GREENWASHING FRAUD. TO THESE EMISSIONS ONE HAS TO ADD THE GREENHOUSE GAS COST OF SMELTING THE STEEL AND ALUMINUM FOR SHIPS AND CONTAINERS AND THE ENERGY USED IN WELDING THEM TOGETHER. CLIMATE BUSTING UNFREETRADE.

Evolution is the Creator. GENERAL THEORY OF UNIVERSAL EVOLUTION. 5 April 2012 Jorma Antero Jyrkkanen, BSC, PDP

My observation that our quarks, gluons and electrons are ancient universe assembled by Physical and Organic evolution into a primate that is now pondering itself, the Parent Universe and Evolution as the Creator is the material foundation for the dawning of a new age of philosophical-scientific-spiritual enlightenment that allows us to be proud and noble in our discovered connection to the our mother universe. We fabricated in far off times imaginary mythical Creator Gods (https://www.godchecker.com/) many in our own image during our pre-scientific genesis. This is I think my most important conclusion. We are the universe. We are the mind of the universe pondering and speaking about itself and have even created a new quasi universe, cyberspace. We are ephemeral and transient and will go extinct one day and return to our quarks, gluons and electrons.

General Theory of Universal Evolution by Jorma Jyrkkanen GENERAL THEORY OF UNIVERSAL EVOLUTION 5 April 2012 My Theory was Presented at the April 12 2012 meeting of The Central Okanagan Naturalists Club to a full house as The Evolution Bit Darwin Couldn't Possibly Know, from Higgs to Comparative Genomics. More has emerged recently on the role of chance and epigenetics. http://www.okanagannature.org/ Thank you ladies and gentlemen for this opportunity to share my limited understanding of this vast subject with you. There are insights here for philosophy, human relations and our relationship with all life and even our place in the universe. A different paradigm emerges from these considerations than the one we have inherited through cultural evolution born in ignorance and mythology. I am humbled by the enormity of it all. PHYSICAL EVOLUTION, THE CREATION OF THE FRAMEWORK FOR ORGANIC EVOLUTION

Big Bang-release of eternal energy, expansion, cooling, 4 Forces peeled off. The laws of the universe emerge with pure energy from the singularity. -Higgs energy field, is everywhere, imparts mass to particles. I like to think of bottom spin on a cue ball stuttering on a rutted table top made of energy density which raises energy of the ball, entangling it with space time which translates into mass. Excitation of the Higgs field is the Higgs Boson. M Theory says strings moving through 11 dimensions causes mass. Einstein E=mc^2 -Since the energy density is the fabric of space time I imagine quantum mechanics is entangled with space time through the Higgs interaction creating the phenomenon Einstein called relativity and which I conjecture imaginatively as gravitational entanglement, the conjugation of quantum mechanics and relativity. -Standard model, quantum mechanics, quantum entanglement and gravity, relativity. It is all about the behavior of energy and how it gathers and interacts. -The DNA of the physical universe is the shape-set of the curled invisible dimensions of string theory. Each shape-set determines the properties of a possible universe. There are 10^500 possible shapes. (I owe this idea to my online Physics Professor, Dr. Leonard Susskind Felix Bloch Professor of Physics, Princeton) -Quark gluon gamma ray soup. The Big Bang diversion via expansion, cooling, layers of the four forces diverge. -Protons and anti-protons form -Symmetry splitting, more protons than antiprotons->proton (matter) universe. They p differ in half lives enabling matter to dominate. Quarks gather in protons and neutrons. Creation of atomic nuclei. -Gases cool, gravity collects into early galaxies and suns. Convergence. -Galaxies, suns, supernovas are born leading to fusion, fission, beta decay nucleosynthesis of elements, periodic table is filled. Our building ingredients mfg'd (O, C, N, S, Fe, Ca, Mg, Na, K, ...) ie created. Creation of new atomic species from gathering protons and neutrons into atoms by electron shells (SPDF orbitals). -Supernovas blow elements into surrounding universe in another Big Bang divergence, expansion carries them off into foamy matrix, gravity collects ejecta into solar systems, planets in another convergence inside galaxies. Supernovas happen every day. Periodic table elements being re-created universe wide constantly. NUCLEOSYNTHESIS OF ATOMS

-Quantum mechanics creates molecules for life both in space and on earth and in space, ex. AA, nucleic acids, ribose. Varieties exist just like with Darwin's finches. -Asteroids, comets deliver molecules of life to planets and some are created by Urey Miller synthesis. In Goldilocks planets there is biomolecular synthesis of AA, proteins, nucleic acids; ongoing also in other regions of the universe in various stages. Combinants converge. Super varieties formed. -Physical evolution creates materials and opportunity for infinite chance events to diversify and a framework for them to happen and exist within. Given infinite time and space and randomness, the least improbable event becomes certitude. -Physical evolution is the creator of the universe and science is the way to know it. We are inseparably part of it all and the energy in our quarks and electrons is as ancient as the big bang, 13.7 bya. -The universe is homogenous enough to assert definitively that these physical evolutionary synthetic processes are broadly similar and universe wide such as to set the stage for organic evolution throughout the cosmos with vagaries of serendipity helping dictate the exact results whence cometh my assertion of the General Theory. Supernovae function vis a vis nucleosynthesis and cooling related force delamination phase changes are likely not affected by modest changes in homogeneity nor isotropy even in an accelerating universe. We are quarks, gluons, electrons and pure energy at root. We are a microcosm of the universe assembled from itself by physica evolution and organic evolution. Physical evolution is the creator of the universe and sets the stage for the evolution of life if chance permits and it does.

ORGANIC EVOLUTION; THE BIOSYNTHESIS OF MOLECULES OF LIFE AND LIFE ITSELF -Urey-Miller biomolecular synthesis, CH4, NH3, H2, H2O, (HCN) -life starts, Pr-Lipid, RNA-Pr lipid, DNA-RNA-Protein, -Watson Crick DNA RNA elucidation as the genetic code of life on earth

ONE THEORY OF ORIGINS Abstract How and where did life on Earth originate? To date, various environments have been proposed as plausible sites for the origin of life. However, discussions have focused on a limited stage of chemical evolution, or emergence of a specific chemical function of proto-biological systems. It remains unclear what geochemical situations could drive all the stages of chemical evolution, ranging from condensation of simple inorganic compounds to the emergence of self-sustaining systems that were evolvable into modern biological ones. In this review, we summarize reported experimental and theoretical findings for prebiotic chemistry relevant to this topic, including availability of biologically essential elements (N and P) on the Hadean Earth, abiotic synthesis of life's building blocks (amino acids, peptides, ribose, nucleobases, fatty acids, nucleotides, and oligonucleotides), their polymerizations to bio-macromolecules (peptides and oligonucleotides), and emergence of biological functions of replication and compartmentalization. It is indicated from the overviews that completion of the chemical evolution requires at least eight reaction conditions of (1) reductive gas phase, (2) alkaline pH, (3) freezing temperature, (4) fresh water, (5) dry/dry-wet cycle, (6) coupling with high energy reactions, (7) heating-cooling cycle in water, and (8) extraterrestrial input of life's building blocks and reactive nutrients. The necessity of these mutually exclusive conditions clearly indicates that life's origin did not occur at a single setting; rather, it required highly diverse and dynamic environments that were connected with each other to allow intra-transportation of reaction products and reactants through fluid circulation. Future experimental research that mimics the conditions of the proposed model are expected to provide further constraints on the processes and mechanisms for the origin of life. This line of work posits the criticality of cyanide, alpha keto acids, ammonia and carbon dioxide.

Research Paper. Origins of building blocks of life: A review; Author NorioKitadai, ShigenoriMaruyama Prior thinking was insprired by the Urey Miller Experiments utilizing methane, hydrogen, water vapour and carbon dioxide and aldehydes. Nucleotides can be created from fairly simple ingredients. -Molecular genetics determines all life has RNA or DNA and RNA and Proteins -Venter and Colleagues elucidate human genome and many many more proving the DNA/RNA based genetic code programs all like on earth and common ancestral origins for all life. -Codification in DNA proves relatedness, degree of similarity in DNA sequence, function relates to degree of relatedness -bacteria earliest life forms (side effect that bacteria feel right at home in us/on us). -bacteria evolved photosynthetic pigments -early bacteria evolved glycolysis ie energy fm sugars -mitochondria bacters (Rickettsias, SAR II) evolved metabolism of pyruvate via citric acid cycle. 36 ATP vs 2 ATP without mitochondria. Mutations in mitochondrial DNA cause myopathies. What we got from our primal bacteria cell merging with mitchondria was energy for work. Primal cell may have also been a ciliate as suggested by oour lung cilia and sperm tails which are near identical to Eukaryote cilia in electron microgrpah cross section. Mitochondrial Endosymbiosis probably with an Archaea cell producing the 3 branches of higher life.

-metazoa evolved by endosymbiosis of p amoeboid cells and mitochondria (SAR II, Ricketsia bacterai) and these evolved into higher animals forms, Protista, Invertebrata, via mergers and acquisitions and lateral transfers, ongoing. -plants evolved by a primal cell merging with endosymbiont mitochondria bacteria and chloroplast bacteria -higher early animals evolved p by Garstang hypothesis process inverts to verts; protogeny of Ascidians, where larva became an adult -Chordates to Vertebrates cephalization with mouth and sensory organs in the front end, gills, jaws, bilateral symmetry, post anal tail, segmented myomeres, cartilagenous notochord, dorsal hollow neural tube, coelom, egenes -Fish (Crossopterigia) evolvedctoderm, mesoderm, endoderm, tissue development by HOX fins into feet and lungs (Dipnoi, lung fish) for gulping air colonizing land as Amphibia -Some Amphibia evolved the amniotic egg that was able to withstand drying conditions forming reptilia and Synapsids which later formed Therapsids and later Mammals and us. A very ancient one found to date was The Hylonomus lyelli, 312 million years old and was discovered in a petrified tree stump near Joggins in the Bay of Fundy, 250 kilometres north of Halifax. The fossil was uncovered by Nova Scotian geologist John William Dawson in 1859 but was handed over to the British Museum around the turn of the century.Apr 24, 2011. Evolution of Amniotes The first amniotes evolved from their amphibian ancestors approximately 340 million years ago during the Carboniferous period. The Amniote Egg.

This is a stem amniote, Protoclepsydrops. Chances are good we once looked like this for a considerable length of time. Looks a tad like Pederpes from the Romer's Gap.

The early amniotes diverged into two main lines soon after the first amniotes arose. The initial split was into synapsids and sauropsids. Synapsids include all mammals, including extinct mammalian species. Synapsids also include therapsids, which were mammal-like reptiles from which mammals evolved. The middle one below is our synapsid ancestor skull form.

-Reptilia ruled til the big asteroid 66.046 million years ago which gave opportunities to mammals. They (Ex Morganuccodon) gave rise to ears, large brains, complex behaviour in mammals w hair, placenta, live immature young, warm blooded, milk and birds. A stem Eutherian (true mammals-our group) Juramia.

Juramaia Skeleton and note dentition had evolved diversity.

- Tree shrew types survived the asteroid to become loris, lemurs, tarsiers, monkeys. Gliding Tree Lemurs as exemplified by the the Colugo are the extant living ancestors of the Primates, our line.

-Those evolved into primates which evolved into us bags of up/down quarks held together w gluons wrapped in whizzy electrons. We invented the Gods to explain how and why but then discovered science, the new how and why. We ponder Higgs, the Genetic code of all life and evolutionary creation.

-Darwin showed surplus production, variants, competition, nature selects, fittest survive. We have since learned about the role of luck. It matters.Primate Evolution produced considerable diversity.

-Venter made a synthetic organism come to life. He picked DNA he wanted, put them together and stuck em in an empty yeast capsule and it worked, did what he wanted. -Geneticists showed populations of genes carried traits and these are acquired from ancestors via linear transfer and also form lateral transfer ex HERV's, bacterial DNA -All living things are kin if you go back far enough. The triplet code for amino acids is constant in all life and this is the strongest evidence all life had a common ancestor and we are all kin, yes evry living thing is kin to us.

-We are a composite of a lot of lateral gene insertions, duplications, mutations, deletions, mergers and and linear injections, a chimaera if you will. All living things are composites. Each merger gave us a set of traits that we have for genetic baggage with fit ones being fixed, bad ones stored, altered or deleted. We are a committee of genomes and genes. -Science is about the creation and the creation process and we could properly call it creation science. -Life begins at the subatomic level when assemblages of quarks begin to cannibalize other assemblages to extract energy and replacement parts. It ceases when the cannibalization stops. SUMMARY OF PHYSICAL AND ORGANIC EVOLUTION INTO THE GENERAL THEORY OF UNIVERSAL EVOLUTION The energy in our atoms is of infinite age and p has always existed by energy conservation laws and needed no creator. Our mother and father were the big bang, supernovas and suns acted upon by gravity, molecular synthesis induced by quantum mechanical effects acting with the four forces, and earth, dashed by asteroids and comets carrying life's molecules, and the organic soup on earth, fired by lightening and fires. A homogenous isotropic universe would have the conditions for life being constantly created by supernovas dispersed approximately as we see spiral galaxies dispersed. this may not be true at boundary conditions. There is an acceleration towards a preferred region of space suggesting periferal anisotropy. The same atoms that are associated with life, and physical processes like nucleosynthesis and quantum mechanics are everywhere in the universe suggesting myriads of opportunities for life elsewhere. Given infinite time and random rolls of the dice the most improbable event becomes certitude. We are a bag of quarks surrounded by electrons causing tiny dimples in space time which in turn gives us our mass through gravity. We spend most of eternity in the atomic and molecular states which only move according to Newton's Laws and a tiny fraction in a virtual mobile form. We can be completely boiled down into three bags, on with up quarks, another with down quarks, a bottle of gluon and a bag of electrons. We are both infinitely old energy, 13+ byo quarks and electrons, atoms of star stuff, created by physical and organic evolution into the mind of the universe, now pondering the universe and our creator, universal evolution. We humans made the thousands of Gods to explain all this before science. All living things are family. The universe is our home and womb, Earth is our heaven. Energy is eternal. All the laws of physics were contained in the singularity. Was it intelligent and benevolent? it was pregnant with possiblity and thats one thing we can count on. Evolution is pretty cruel from time to time and flawed so its hardly benevolent. So what are humans and why are we here? I call this the cypher. The how is the why and science explains how and this tells us why things are what they are. To know why, find out how. It answers an enoromous philosophical void. https://humanorigins.si.edu/education/introduction-human-evolution WHAT THEN ARE WE HUMANS? 1 March 2012 The energy in our atoms is of infinite age and p has always existed by energy conservation laws and needed no creator. Our mother and father were the big bang, supernovas and suns acted upon by gravity, molecular synthesis induced by quantum mechanical effects acting with the four forces, and earth, dashed by asteroids and comets carrying life's molecules, and the organic soup on earth, fired by lightening and fires. A homogenous isotropic universe would have the conditions for life being constantly created by supernovas dispersed approximately as we see spiral galaxies dispersed. this may not be true at boundary conditions. There is an acceleration towards a preferred region of space suggesting periferal anisotropy. The same atoms that are associated with life, and physical processes like nucleosynthesis and quantum mechanics are everywhere in the universe suggesting myriads of opportunities for life elsewhere. Given infinite time and random rolls of the dice the most improbable event becomes certitude. We are a bag of quarks surrounded by electrons causing tiny dimples in space time which in turn gives us our mass through gravity. We spend most of eternity in the atomic and molecular states which only move according to Newton's Laws and a tiny fraction in a virtual mobile form. We are both infinitely old energy, 13+ byo quarks and electrons, atoms of star stuff, created by physical and organic evolution into the mind of the universe, now pondering the universe and our creator, universal evolution. All living things are family. The universe is our home and womb, Earth is our heaven. Energy is eternal. All the laws of physics were contained in the singularity. Its likely chance alone enabled life in our universe? it was pregnant with possiblity and thats one thing we can count on. Evolution is pretty cruel from time to time and flawed so its hardly benevolent or intelligent. It just works like a hot dam. Physical and organic evolution, universal evolution, are the creator, governed by the laws of nature. We are e the universe become conscious pondering itself. We are the mind of the universe in very real sense. We made stories in mythology and the gods to explain the how and why and now science teaches us how the laws of nature made everything from energy. I dedicate this Theory to my Late Brother Dougy Jyrkkanen wo died in a tragic accident as a Youth. We discussed investigation of this topic when paddling down the Skagit River in a raft while doing phenology and deer studies for Slaney while I was a Zoology student at UBC.

Copyright 2012 Jorma Jyrkkanen. All rights reserved. Tags: Evolution, physical evolution, organic evolution, General Theory of Universal Evolution, Jorma Jyrkkanen

Antibiotics Discussion. Risks and Benefits. Mitochondrial Poisons? Discussion by Suárez-Rivero JM, Pastor-Maldonado CJ, et al. 2022-10-25. Jorma Jyrkkanen

The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed.

Suárez-Rivero JM, Pastor-Maldonado CJ, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I, Talaverón-Rey M, Suárez-Carrillo A, Munuera-Cabeza M, Sánchez-Alcázar JA. Mitochondria and Antibiotics: For Good or for Evil? Biomolecules. 2021 Jul 17;11(7):1050. doi: 10.3390/biom11071050. PMID: 34356674; PMCID: PMC8301944.

Jobs recommended to me from ResearchGate.org. 2022-10-22. Jorma yrkkanen

CAN WE BOOST MITOCHONDRIAL NUMBER IN A WAY CONSISTENT WITH ORIGINAL CELLULAR TISSUE TYPE FUNCTION? THOUGHTS. 2022-10-21

IS IT POSSIBLE TO REPLACE DAMAGED MITOCHONDRIA PHARMACOLOGICALLY?

Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem. 2010;47:69-84. doi: 10.1042/bse0470069. PMID: 20533901; PMCID: PMC3883043. CAN WE FACILITATE MITOGENESIS BY PROTEIN DEFICIENT FASTING? CAN WE INTRODUCE OR BOOST AMPK PRODUCTION TO STIMULATE MITOGENESIS NUMBERS CONSISTENT WITH CELL DEFICIENCY AND TISSUE SPECIFIC REQUIREMENTS? CAN WE PHARMACOLOGICALLY BOOST MITOGENESIS TO PROVIDE FOR LOSSES TO ANTIBIOTICS, PESTICIDES AND COVID AND OTHER BIOCIDES? iT OCCURS TO ME WE ARE ONLY AS OLD AS OUR MITOCHONDRIA?

Dr. Tent Gave Evidence the Autoimune Epidemic was in Fact Caused by Viruses. Commentary Resulting. 2022-10-20. Jorma Jyrkkanen

Inner Connections>Welcome to Inner Connections>Cafe>Cafe, Fun Things Archived> The Exploding Autoimmune Epidemic - Dr. Tent - It's Not Autoimmune, you have Viruses. Crochet Sue IC Angel Jan 29, 2013#1 The Exploding Autoimmune Epidemic - Dr. Tent - It's Not Autoimmune, you have Viruses. This is about vaccines, they contain viruses that cause all kinds of diseases. I am watching this video and it is very interesting. It's 2 hrs long and I realize most do not have the time to watch it so I'm taking notes. I was taking notes for one of my sisters, and decided to post them here too. I have only watched a half hour so far and will post the notes I took below. I will post more as I watch it, which I won't be watching anymore tonight, but over the next few days. In this first half hour he is talking about the vaccines causing cancer. He hasn't talked about vaccines causing autoimmune diseases yet. I am interested to get to that part as scleroderma, which Gabby had, is also an autoimmune disease that starts out the same as arthritis but gets much worse when it attacks internal organs. Quote Share Jan 29, 2013#2 Notes from the first half hour: They thought a virus was the cause of cancer in the early 50's In 1999 to 2001, 60 Minutes investigated this story and they put more money and time into than any other story they ever aired. They said there is no way they can air this so they didn't. 1942 antibiotics were released, 1943 polo became an epidemic. Polo mimicked the flu so people were treated with antibiotics when they really had polo. 1955 a polo vaccine was rushed into productions. They put formaldeyde in the vaccine. Dr. Bernice Eddy said they should test it first, she tried it on monkeys and they were paralzed. She tried to get them to halt the vaccine but they did it anyway. Kids got sick from polo and were paralzyed. The polo vaccine never stopped polio, it was stopped by people practicing better santitation and refrigeration methods. Dr. Eddy was taken off the polio research. She and Dr. Sarah Stewart discovered that cancer is caused by a virus. The vaccine manufacturers were growing their polio viruses on the kidneys of monkeys and when they removed the polio virus from the monkey kidneys they also removed an unknown number of other monkey viruses with it. In 1959 Dr. Bernice Eddy found overwhelming evidence that they had just inoculated an entire generation with cancer-causing monkey viruses. She predicted an epidemic of cancer. There is 40 monkey viruses in the vaccines. The government made it classified and would no longer allow information about it out to the public. Everyone still has these viruses from the vaccines inside of them. If you get a blood sample analyzed they would find these viruses in it. In 1960 Dr. Bernice Eddy gave a talk to the New York Cancer Society and announced that she examined the monkey kidney cells in which the polio virus was grown and found they were infected with cancer-causing viruses, SV-40. They crushed Bernice Eddy professionally. They took away her lab, destroyed her animals, put her under a gag order and delayed publication of her scientific papers. In 1961 federal regulations went into effect that required that the polio vaccines be free of SV40 but they did NOT require the SV40 contaminated seeds used to make every batch or lot of vaccine be discarded nor the recently manufactured contaminated vaccines be discarded. They continued giving the contaminated vaccines to children and adults until they were used up sometime in 1963. In 1962 Sabin Oral Polio vaccine is introduced but they used the same culture medium, the monkey kidneys. This was the vaccine put into the sugar cube that everyone took back then. It is estimated that 1 out of every 200 people are getting cancer caused by SV40. They started to realize that cancers rarely seen such as lung, breast, prostate, lymphoma, brain and melanoma increased 50% over a 16 year period. Lung cancer is rising because the vaccine is causing it, not smoking. As smoking has gone down, lung cancer has gone up. The vaccine developers did not want to release this information. They said it would scare the public unnecessarily. If they hear that their children were injected with a cancer virus that would not be very good. Men born between 1948 and 1957 have 3x as much cancer not related to smoking. The study's researchers insist the increase cannot be explained by smoking, better diagnosis or an agin population. Public Health Official, Devra Lee Davis said "There's something else going on here." The SV40 virus is also sexually transmitted and you can get it from a blood transfusion and it is spread from mother to child even if they had never got the vaccine shots. Those never inoculated with the contaminated vaccine inherits it up from their parents and can pass it on or infect their children and grandchildren. This information has been blacked out from history. Their is also a virus in the vaccine that acts like AIDS. Robert Gallo's group at the NCI and Litton Bionetics also experimented with other simian and human cancer viruses (e.g., SV40), and developed recombinants (i.e. mutants) of these with other viral nucleic acids including those that caused the prominent features of AIDS -- WBC dysfunction, leukemias, lymphomas, sarcomas, progressive wasting, and ultimate death in cats, mice, chickens, and humans. All this in the likely presence of other easily mutated retrovirus contaminents. This is what they were manufacturing.

Bisulfite induced P53 gene mutation of G:C--->A:T Probably leading to lung cancer Partial Explanation of one Cancer Increased in Pulp industry Communities. Jan 18 2013 Jorma Jyrkkanen

Bisulfite induced P53 gene mutation of G:C--->A:T Probably leading to lung cancer Partial Explanation of one Cancer Common in pulp industry? Jorma's News Old Story Monica Hollstein et al. (1991) mentioned that the most common mutation in lung cancer in the P53 gene is G:C--->A:T (found in 46% of small cell lung cancers and 57% of non-small cell lung cancers). A reference of hers and others of interest http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827900/. While conducting a pulp mill air emissions health effects literature review for the Al-Pac hearings in Alberta, I found a reference to bisulfite ion ie. sulfur dioxide SO2 transforms into bisulfite ion HSO3- in T4RII Phage causing G:C--->A:T mutations (Lawrence Fishbein, 1976, Atmospheric Mutagens. 1. Suflur Oxides Plus Nitrogen Oxides. Mutation Research (32):309-330.). Fishbein reports that bisulfite was mutagenic to viruses, bacteria and plants, and that it was a moderately strong mutagen. Low levels increased chromatid aberrations and fragments,laggards, and micronuclei were often observed. Clumping at 5 ppm inhibited mitosis. Here is a mutagen that inhibits mitosis but is linked to cancer. Here is the Fishbein reference hidden from the poor of the world behind a $31.50 Paywall. http://www.sciencedirect.com/science/article/pii/016511107690004X Sulfur dioxide depressed DNA synthesis and growth and increased abnormalities in human lymphocytes [HeLa Cells]. In the mouse, Ewe, and Cow Oocytes, the alterations resulted in transmitted genetic disorders. Fragmentation, rearrangements, anaphase laggards, all led to aneuploidies {altered chromosome numbers} resulting in fetal losses and congenital abnormalities. The mammalian mutations are noteworthy and raise the flag for humans on potential similar effects. I would suspect that these pollutants abilities do not stop here and could probably account for many more illnesses. Do we have here an almost complete environmental explanation of a genetic change leading to cancer in humans? After reading the two articles I proclaimed that bisulfite was involved in causing lung cancer. I had not seen the link made previously. In retrospect (2013) it has been found that frank carcinogens can cause single step carcinogenesis while multiple defects and mutations are involved in cases where weaker carcinogens are involved. Because this mutation is involved in less than 100% of lung cancers bisulfite likely falls into the multiple mutation carcinogenesis. IARC lists bisulfite as a Class 3 carcinogen (http://en.wikipedia.org/wiki/List_of_IARC_Group_3_carcinogens). CDC does not list it (http://www.cdc.gov/niosh/topics/cancer/npotocca.html). I was therefore wrong in proclaiming bisulfite causes cancer because it now seems more likely it is just one step in the sequence of defects leading to cancer. The ramifications for carcinogen management and regulation are more clear however. Mutagens must be regarded as carcinogens because any one of them can be the one that causes the final mutation leading to cancer, ie the straw that breaks the camels back. Copyright 1991 Jorma Jyrkkanen. All rights reserved.

The Probable Reason TREX had Small front Limbs. 2022-10-19. Jorma Jyrkkanen

It has long remained a puzzle why TREX has small front limbs.I think I know the answer.

Eggs need to be turned every day to aid in embryo development. There is no other appendage suitable but the small forelimbs and possibly the mothers tongue. We see raptors turning eggs with their bills today so we know it is a vital part of egg care. Poultry breeders Turn the eggs during incubation prevents embryo death and unhealthy hatches. Eggs must be turned at least five times every 24 hours. Turning more frequently is better and once per hour is best. Ergo small forelimbs ensure healthy Baby TREX hatches. This is my 230th Archival Blog Post. Copyright 2022-10-19 Jorma Jyrkkanen

Physiological Adaptation in the Neoproterozoic to Early Cambrian to Dynamic Oxygen Fluctuation Challenges Enabled Respiratory Evolution. Oct 2022 Jorma Jyrkkanen

Christopher Clifford 33m · Dynamic Oxygen Levels May Have Accelerated Animal Evolution: "The question scientists have tried to answer is - was there anything extraordinary about the changes to oxygen levels in the Neoproterozoic Era that may have played a pivotal role in the early evolution of animals – did oxygen levels suddenly rise or was there a gradual increase? Dr Benjamin Mills, who leads the Earth Evolution Modelling Group at Leeds and supervised the project, said: “This periodic change in environmental conditions would have produced evolutionary pressures where some life forms may have become extinct and new ones could emerge.” “When oxygen levels decline, there is severe environmental pressure on some organisms which could drive extinctions. And when the oxygen-rich waters expand, the new space allows the survivors to rise to ecological dominance. “These expanded habitable spaces would have lasted for millions of years, giving plenty of time for ecosystems to develop.” Extreme variability in atmospheric oxygen levels in the late Precambrian Alexander J. Krause https://orcid.org/0000-0002-9771-8101 , Benjamin J. W. Mills https://orcid.org/0000-0002-9141-0931, Andrew S. Merdith https://orcid.org/0000-0002-7564-8149, Timothy M. Lenton https://orcid.org/0000-0002-6725-7498, and Simon W. Poulton https://orcid.org/0000-0001-7621-189X Science Advances 14 Oct 2022 Vol 8, Issue 41 Abstract Mapping the history of atmospheric O2 during the late Precambrian is vital for evaluating potential links to animal evolution. Ancient O2 levels are often inferred from geochemical analyses of marine sediments, leading to the assumption that the Earth experienced a stepwise increase in atmospheric O2 during the Neoproterozoic. However, the nature of this hypothesized oxygenation event remains unknown, with suggestions of a more dynamic O2 history in the oceans and major uncertainty over any direct connection between the marine realm and atmospheric O2. Here, we present a continuous quantitative reconstruction of atmospheric O2 over the past 1.5 billion years using an isotope mass balance approach that combines bulk geochemistry and tectonic recycling rate calculations. We predict that atmospheric O2 levels during the Neoproterozoic oscillated between ~1 and ~50% of the present atmospheric level. We conclude that there was no simple unidirectional rise in atmospheric O2 during the Neoproterozoic, and the first animals evolved against a backdrop of extreme O2 variability. Mechanisms of Adaptation Jorma Jyrkkanen Blood stem cells today in mammals have the ability to produce more when challenged by oxygen deficit. Secondary polycythemia most often develops as a response to chronic hypoxemia, which triggers increased production of erythropoietin by the kidneys. This kind of condition may have early antecedents in the Neoproterozoic facilitating adaptation to hypoxia challenge and enabling higher respiratory processes to evolve. Looking for evidence of this capability in more primitive phyla might yield important clues to what exactly happened to improve respiratory adaptation. I suspect mitochondria also improved during this time. Oxygen is central to aerobic respiration—it is the terminal electron acceptor of the mitochondrial electron transport chain (ETC), which transfers electrons from high energy metabolites through a series of carriers to drive ATP generation from ADP. The ability to increase mitochondria in hypoxia challenge may have also facilitated Neoproterozoic respiratory adaptation. These oxygen fluctuations would have created ideal situations for aerobic glycolysis, anaerobic glycolysis, and pyruvate fed xidative phosphorylation metabolisms at various times not to mention ideal situations for alternate metabolisms like methane and CO2 drives. Cancer cells today operate optimally on glycolysis suggesting they may have originated in this dynamic gas fluctuation era.

We Were Made Possible by a Symbiotic Fusion of Two Prokaryotes about 1.8-2 bya Like Plants Which Also Acquired Phtosynthetic Endosymbionts. 2022-10-14 Jorma Jyrkkanen

ORIGIN OF MITOCHONDRIAMitochondria originated by permanent enslavement of purple non-sulphur bacteria. These endosymbionts became organelles through the origin of complex protein-import machinery and insertion into their inner membranes of protein carriers for extracting energy for the host. Mitochondria originated by permanent enslavement of purple non-sulphur bacteria. These endosymbionts became organelles through the origin of complex protein-import machinery and insertion into their inner membranes of protein carriers for extracting energy for the host. THE PROKARYOTE MICROBES THAT ENGULFED PURPLE NON-SULPHUR BACTERIA Archaea were the most likely candidate. In particular, The origin of eukaryotes remains unclear1,2,3,4. Current data suggest that eukaryotes may have emerged from an archaeal lineage known as ‘Asgard’ archaea5,6 (Isolation of an archaeon at the prokaryote–eukaryote interface. Hiroyuki Imachi, Masaru K. Nobu. 15 January 2020) EVIDENCE TO SUPPORT THIS THEORY OF THE EARLY ORIGIN OF HIGHER LIFE(Organismal Biology) Mitochondria (and chloroplasts) are approximately the same size as prokaryotic cells, but they are located inside much much larger eukaryotic cells instead of free-living. Mitochondria (and chloroplasts) each have their own DNA, their DNA is organized in a circular chromosome like typical prokaryotic genomes, and their genomes contain genes that are very similar to genes found in prokaryotic genomes. Mitochondria (and chloroplasts) reproduce by binary fission, the process that prokaryotes use to reproduce. In contrast, eukaryotic cells reproduce by mitosis. If the mitochondria (or chloroplasts) are removed from a eukaryotic cell, the cell has no way to produce new ones. In other words, the “instructions” to make new mitochondria/chloroplasts is not present in the eukaryotic nuclear genome; they are present in the mitochondria/chloroplast genomes. The membrane composition of mitochondria (and chloroplasts) is more similar in composition to prokaryotic membranes than to eukaryotic membranes.

Impact of Antibiotics on Mitochondria Increase Risks of Cancer, Heart Disease, Failed Immune system and Other Medical Problems. JCCM 2 Oct 2020. Jorma Jyrkkanen.

https://www.heighpubs.org/jccm 163https://doi.org/10.29328/journal.jccm.1001104 Research Article Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks Jorma Jyrkkanen* British Columbia, Canada More Information *Address for Correspondence: Jorma Jyrkkanen, British Columbia, Canada, Tel:1-250-859-5330; Email: jormabio@hotmail.com Submitted: 17 August 2020 Approved: 01 October 2020 Published: 02 October 2020 How to cite this article: Jyrkkanen J. Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks. J Cardiol Cardiovasc Med. 2020; 5: 163-171. DOI: 10.29328/journal.jccm.1001104 Copyright: © 2020 Jyrkkanen J. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Keywords: Antibiotic; Mitochondria; DNA damage; P53 tumor suppressor cene; Mutp53; ROS; Lipid peroxide; Cell perforation; Cell rupture; Oxidative phosphorylation; Cancer; Carcinogenesis; Glycolysis; Warburg effect; Microbiome; Dysbiosis; Immune suppression; Pesticides; Mechanism; Clastogenic; Epigenetic silencing; Microrna; DNA; Heart OPEN ACCESS Abstract With the discovery by Calghatgi (2013) that three common antibiotics (Abs) increased mitochondrial reactive oxygen (ROS) and lipid peroxide (LP) and depleted their natural absorbant glutathione led me to investigate further the potential impacts of these genotoxic substances on carcinogenesis. The range of impacts on mitochondria and cellular DNA varied by antibiotic to those consistent with known prior contributions to carcinogenesis. Specific cancers probably increased by these changes were HCC, RCC (KCC), CRC, cancer of the esophagus. Tumor suppressor gene mutations resulting from LP were noteworthy in this regard and mutations induced in CRC were consistent with those found in carcinogenesis of CRC. In addition depression of short chain fatty acids in microbiomes were found which depress the immune system increasing risk of all cancers. Many cancers were increased according to epidemiological studies linking Abs with elevated odds ratios, with one concern in particular, fatal breast cancer. The impact of loss of functionality of the mitochondria was also linked to depression of the citric acid cycle and therefore ATP which deflected metabolism to glycolysis, the Warburg mechanism also increasing risk of all cancers, favoured by cancer cells. In conclusion, some portion of many cancer types are probably increased in likelihood by number, type and frequency of Abs treatment and chronic residue exposure which varies from individual to individual. This led me to propose a three pronged carcinogenesis mechanism for Abs. 1. Cancer critical mutations 2. Immune depression 3. loss of mitochondrial functionality leading to Warburg effects. Damage to mitochondria were also noted by common pesticides tested in China and cancer associations were also found for many pesticides supporting a similar contributory etiology. Heart health concerns were raised by these findings because of the myriad mitochondria in the heart and because of long term reliability needs. Studies suggesting hearts were affected by Abs and pesticide exposure were presented. Because of their geographical ubiquitousness and the huge range of diseases associated with mitochondrial dysfunction, antibiotics and pesticides and bacteriocidal biocides are of concern for biodiversity and life in general. I propose research steps to evaluate Abs safety and suggest directions for further research and make suggestions on ways to ameliorate Abs toxicity. Introduction Antibiotics kill or slow the growth of bacteria or interfere in their reproduction. The mitochondria, an ancient alpha- proteobacteria [Rickettseae] that has become an endosymbiont in higher life forms with critical functions, response to them has been found to be a decrease of beneβicial antioxidant glutathione, increased reactive oxygen, increased harmful lipid peroxide, possible DNA damage and mutations in tumour suppressor genes increasing cancer risk, possible inability to reproduce, possible cell perforation and or rupture. Some antibiotics have been shown in the past to be clastogenic. These types of responses have broad biochemical and health implications. They could lead to carcinogenisis, microbiome dysbiosis with resulting immune system depression and or loss of oxidative phosphorylation (OP) favouring glycolysis metabolism which is also the favoured method for cancer cells. Changes could enhance the Warburg effect favouring cancers. P53 genes may be turned off epigenetically at the DNA. Defective mitochondria have been implicated in over Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks https://www.heighpubs.org/jccm 164https://doi.org/10.29328/journal.jccm.1001104 200 medical conditions. In addition a big unknown is the relationship between which biocides may epigenetically shut down critical genes found with each particular kind of cancer. Clinical and epidemiological evidence supports the conclusion that some antibiotics are carcinogens, others promote cancers and cancer risk increases with frequency and type. Microbiome dysbiosis and immune depression risk is increased. While exposure may not complete all the steps to cancer it may contribute important mutations along the way. Other life time exposures can can complete the process. Chinese researchers recently found that a high proportion of common pesticides ruptured mitochondria like some antibiotics. Individuals who were exposed to pesticides were more than twice as likely overall to have conditions like heart disease, heart failure or an irregular rapid heartbeat known as atrial βibrillation [1]. It can be inferred that ruptured mitochondria from antibiotics would lead to similar coronary pathologies. There is reason to suspect that all Eukaryotes are subject to pathological impacts. The mitochondria enabled multicellular evolution to higher forms of life and is now under attack worldwide by anthropogenic biocide pollution. More research is needed to determine which of all biocides is mitochondria friendly, enables them to be fully functional without mutations, prior to regulatory approvals. I propose an antibiotic mitochondria carcinogenesis mechanism. For a general overview of impacts of antibiotics on total general physiology and health of ecosystems including plants see Wang, Xu et al. [2]. A criticism of some βindings is that people with cancer are more prone to infections and this can account for much of the association of antibiotics with cancer [3]. However the βinding of immune compromise is consistent with antibiotic induced microbiome associated dysbiosis. Mitochondrial job and creation of toxic mix by antibiotic Mitochondria, a primitive endosymbiotic bacteria, related to extant SARII marine bacteria and Rickettsias, in eukaryotes is responsible for OP resulting in ATP and NAD production for energy. When exposed to clinically equivalent doses of antibiotics that target bacteria (cipromycin, ampicillin, kanamycin), exhibited a decline in glutathione titre, an increase in reactive oxygen (ROS) and an increase in lipid peroxide with damage to DNA and potential mitochondrial rupture [4]. Tetracyclines used for humans and livestock have also been linked to mitochondrial genetic damage [5]. Some antibiotics have been found to be break chromosomes [6]. Modes of action of antibiotics on mitochondria and microbiome 1. quinolones- commonly prescribed antibacterial organoβluorine compounds which act by inhibition of bacterial DNA synthesis and result in rapid cell death [7]. This group contains oβloxacin, norβloxacin (noroxin), ciproβloxacin (Cipro), moxyβloxacin (Avelox). Expectation is to obstruct mitochondrial replication. Norβloxacin demonstrated a linear antibiotic-DNA mutation rate, compromised DNA oxidative damage repair and post replicative mismatch repair [8]. They could be expected to do similar collateral damage to mitochondria and to members of the human microbiome. 2. aminoglycosides-ex gentamicin, amicasin which create holes in the outer cell wall of bacteria suggesting mitochondria and the microbiome might be at risk of similar damage [9]. Damage to lipid membranes can be expected. Lipid membranes have wide distribution in both microbes and other animals including humans. 3. β-lactams or penicillin derivatives such as cephalosporins, monobactams, carbapenems, carbacephems inhibit cell wall synthesis in bacteria and by inference inhibit cell wall synthesis in mitochondria during division and repair and microbiomes thereby obstructing microbial reproduction. Penicillamine is listed as a ‘developmental’ in California Proposition 65. 4. Tetracyclines-used on cattle and humans and possibly acquired secondarily as dietary residues may affect mitochondria because they speciβically target Rickettsias a probable evolutionary ancestor [2,10.11]. 5. Anthracyclines-result in clastogenicity [6]. Harmful impact of liberated substances on DNA, P53 tumour suppressor gene, mutagenicity and known effects in other cancers Glutathione is an antioxidant that soaks up ROS and is essential for many neurological and other body functions. Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals. Genomic instability occurs in myeloid malignancies with increased reactive oxygen species ROS, DNA double strand breaks (DSBs) and error-prone repair [12]. ROS linked to many cancers by oxidative DNA damage “numerous studies have shown generation of reactive oxygen species (ROS) that can cause oxidative damage of DNA. This is a well-known mechanism in carcinogenesis for many agents” [13]. Excessive levels of ROS accumulation due to altered equilibrium between ROS and antioxidants may lead to different kinds of diseases such as atherosclerosis, diabetes, neurodegeneration, and cancer including CRC. It is widely known that ROS-induced DNA damages and genetic mutations are critical causes of cancers including CRC. The main intracellular DNA lesions caused by ROS are single and double strand DNA breaks, and the common genetic mutations include p53, KRAS, APC, and BRAF mutations often seen in CRC’s. For example, a direct relation among oxidative stress, DNA damage and elevated frequency of p53 mutation in CRC Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks https://www.heighpubs.org/jccm 165https://doi.org/10.29328/journal.jccm.1001104 has been observed. Most extensively studied endogenous DNA damage by ROS is the formation of 8-oxo-7,8-dihydro- 2’-deoxyguanosine (8-oxodG). As the biomarker of oxidative stress, 8-oxodG level is higher in colorectal tumors than in normal mucosa. Mitochondrial DNA is particularly prone to be oxidatively damaged and is more meaningful in colorectal carcinogenesis [14]. I would expect antibiotic induced drop in antioxidant glutathione to contribute to such an altered equilibrium and assay for 8-oxodG post antibiotic treatment might be a good indicator of antibiotic carcinogenic potential as well as looking for deβicits of ATP, an indicator that metabolism has switched to cancer cell loving glycolysis from pyruvate metabolism. Lipid peroxide associated cancers Besides being generated by mitochondria exposed to antibiotics, lipid peroxide is also increased with analgesics like aspirin (though some studies show it reduces LP) and NSAIDS naproxin, indomethacin and diclofenac, being male, among hypertensives, diabetics, smokers, oophorectomized and pregnant women especially with eclampsia and pre- eclampsia [15]. Ochratoxin a mycotoxin found in cereals and grains also increases LP. These mutiple sources need assaying when making links to antibiotics impact on mitochondria. Lipid peroxide has been linked to esophageal carcinogenesis [16] and to red meat and treated meat colon carcinogenesis [17]. The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma [18]. In a seemingly unrelated exposure from aβltoxin researchers report an increased frequency of loss of the Hae III allele and base G mutation on p53 gene at codon 249 where it is mutated to C [19]. Why this matters is because this same P53 gene locus is linked to HPV cervical cancers from a study done on Kenyan women [20]. HPV cancers are associated with genital, anal and oral tissues. Antibiotics production of lipid peroxide and its metabolites can also mutate this gene locus and that is found with HCC. Lipid peroxidation has been proposed as a mechanism for renal cell carcinoma RCC [15]. Based on their work I added my comments. Lipid peroxide (LP) degrades into mutagens that target tumor suppressor gene p53 and may alter functionality of other tumor suppressor genes like VHL speciβically linked to hereditary RCC and is postulated by me and the latter authors to be a carcinogen linked to renal cell carcinoma. I phrase this as a question. Lipid peroxide is generated by antibiotics attacking mitochondria which then release it into the tissue environment and may even rupture cells in the process. I recommend an investigation to study additionally antibiotic history in regards to VHL depressed kidney cancer. The placenta is the main source of LP in pregnant women. Look also at Aspergillis and ochratoxin A as a mutagen for the TSG genes involved. The following article hints at LP causality. Fumonisims, a fungus in corn and other grains is linked to kidney cancer and is possibly acting through mutation of the p53 gene. P53 overexpression has been correlated with increased RCC. Inactivation of the VHL TSG is responsible for polycystic kidney disease and for renal cell carcinoma of the hereditary VHL cancer syndrome and for the majority of sporadic renal cell carcinomas. Protectively, polyphenolics in red wine are postulated to soak up the lipid peroxides and reduce RCC risk. Estrogens especially 2-hydroxyestradiol, mannitol, SOD and vitamin E are all LP sponges along with the mitochondrial glutathione. This suggests antibiotics are a cofactor in carcinogenesis of several if not multiple cancers via this same p53 locus 249 mutation’s contribution or by lipid peroxide contribution and ROS contributions to reduce TSG DNA repair and function. Lipid peroxide metabolite hydroxy-2-nonenal is also found in red meat and treated meat carcinogenesis. It is safe to conclude that antibiotics are one cause of or major contributing factor to hepatocelluar carcinoma and are also potentially involved in colon carcinogenesis. In CRC, the commonest lipid peroxidation products are MDA and HNE, the levels of which in the CRC tissue are signiβicantly increased with clinical staging [21]. CRC and RCC are likely to be cancers potentially associated with antibiotic mitochondrial disruption. P53 changes associated with warburg effect Possible P53 gene upregulation (PUMA->WTP53) may lead to the Warburg effect favouring cancer [22]. Proximicins A, B, and C—antitumor furan analogues of netropsin from the Marine Actinomycete verrucosispora induce upregulation of p53 though I am not certain this is the same effect as PUMA [23]. Mutated P53 actually becomes the mutP53 guardian of cancer cells [24]. Normal function of p53 blocked by loss of mitochondria through damage or rupture Tumor suppressor p53 plays a central role in tumor prevention. As a transcription factor, p53 mainly exerts its function in tumor suppression through its transcriptional regulation of its target genes to initiate various cellular responses. Cell cycle arrest, apoptosis and senescence are most well- understood functions of p53, and are traditionally accepted as the major mechanisms for p53 in tumor suppression. Recent studies have revealed a novel function of p53 in regulation of cellular metabolism. p53 regulates mitochondrial oxidative phosphorylation, glycolysis, glutamine metabolism, lipid metabolism, and antioxidant defense. Through the regulation of these metabolic processes, p53 maintains the homeostasis of cellular metabolism and redox balance in cells, which contributes signiβicantly to the role of p53 as a tumor suppressor [25]. Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks https://www.heighpubs.org/jccm 166https://doi.org/10.29328/journal.jccm.1001104 P53 Cell guardianship and critical OP obviously cannot happen if the mitochondria is ruptured or defective or if the p53 gene has been mutated, silenced or sequestered to assist cancer cells. With diminished OP, Warburg effects will increase and cancer cells will be given a boost. This might well be a serious collateral impact of antibiotics. Antibiotics render the immune system less effective in infection Researchers reporting in Frontiers in Microbiology found that short chain fatty acids (SCFA) from resident bacteria were important in protecting the immune system, and inβlammation control. Both of these side effects have important ramiβications for prevention of cancer initiation. Antibiotics diminished resident bacteria carrying out this role and supplemental SCFA were not effective in ameliorating the effect. Dysbiosis of resident microbes is unequivocally associated with immune-related disorders and opportunistic and pathogenic infections which can themselves set the stage for cancer [26]. If potentially carcinogenic microbes Helicobacter pylori, Streptococcus bovis, Salmonella typhae, Fusobacterium, Chlamydophyla, Bartonella or Caries bacteria or any carcinogenic viruses such as EBV, HPV, alpha-HPV, beta-HPV, HHV, HBV, HVC, KSHV and possibly retroviruses or Schistosomes and liver βlukes facilitated by [27] depressed immune systems proliferate as a consequence this can lead to increased incidence of cancers especially the viral cancers which do not respond to antibiotics but will take advantage of a depressed immune system. Along this line there has been an increase in oropharyngeal HPV cancers in Canadian men [28]. The depressed immune system may also lessen the bodies ability to kill cancerous cells regardless of their etiological origins. Another of the consequences of antibiotic use is development of antibiotic resistance. One of the carcinogenic bacteria, H. Pylori is an example [29] the consequence of which may lead to an increase in stomach cancers in developed countries unless we can come up with new more effective mitochondria friendly antibiotics. The evidence of carcinogenesis from research Seeing that these changes were consistent with steps found in carcinogenesis [30] I asked the question, what is the clinical and epidemiological evidence that antibiotics increase the risk of cancer? It appears others have also addressed this question [31,32], [antibiotic use predicts an increase in the risk of cancer]; I reproduce Kilkkinen’s results because they speak to the range of cancers brought under suspicion. “The use of antibiotics was associated with an increased risk of cancer; for categories of increasing antibiotic use (0–1, 2–5 and #6 prescriptions), RRs (95% CIs) were 1.0 (reference), 1.27 (1.26–1.29) and 1.37 (1.34–1.40). The association was found both in men (RR for comparison of lowest and highest exposure group 1.47, 95% CI 1.42–1.53) and women (RR 1.31, 95% CI 1.28–1.35). The most common cancers i.e. prostate, breast, lung and colon comprised half of all cancer cases; RR (95% CI) was 1.39 (1.31–1.48) for prostate, 1.14 (1.09–1.20) for breast, 1.79 (1.67–1.92) for lung, and 1.15 (1.04–1.26) for colon cancer. RRs for other primary sites varied between 0.90 (0.76–1.05) for ovary and 2.60 (1.60–4.20) for endocrine gland cancers. In addition to endocrine gland and liver cancers, the risk of non-melanoma skin, duodenum, pancreas, kidney, bladder, male genitals (excluding prostate) and thyroid cancers as well as myeloma and leukemia was more than 1.5 times higher among participants with 6 or more antibiotic prescriptions compared with the lowest exposure group. Restricting analyses to participants with 5 or more years follow-up did not produce signiβicantly different results from those covering the entire study population (RR for the comparison of lowest and highest exposure group 1.37, 95% CI 1.34–1.40). Similar results were obtained when the data were stratiβied according to age (data not shown). We also observed an increased risk of death due to cancer with use of antibiotics (RR 1.33, 95% CI 1.28–1.38). There was a similar tendency for an increased cancer risk with annual antibiotic use (table is available from authors by request). Compared with non-users of antibiotics, RRs (95% CI) for 1 year,2 and 3 years of use were 1.33 (95% CI 1.32–1.35), 1.40 (1.38–1.42) and 1.46 (1.43–1.49), respectively. RRs (95% CI) for 3 years of use for different primary sites varied from 0.99 (0.86–1.14) for ovary to 1.81 (95% CI 1.62–2.02) for non-melanoma skin cancers and was 1.21 (1.15–1.26) for breast and 1.57 (1.49– 1.66) for prostate cancers.” Tim Newman 2017 [33] [antibiotics may increase the risk of bowel cancer]; Millipore-Sigma 516104 [34]. [penicillin/streptomycin/amphotericin-harmful, teratogenic and carcinogenic]). Velicer et al. [35] found prolonged use of antibiotic increased risk of fatal breast cancer. This has broad global ramiβications because of the chronic long term exposure of antibiotic residues in diet from treated foods such as beef, pork, poultry and farmed βish and sea food products. In a new epidemiological study ‘intakes of dairy calories and dairy milk were associated with BC hazard ratios (HRs) of 1.22 [95% conβidence interval (CI): 1.05–1.40] and 1.50 (95% CI 1.22–1.84)’ [36]. These results are deeply troubling despite any experimental difβiculties because they almost unanimously point in the same direction to increasing carcinogenicity and the huge global populations exposed to residues. Zhang et al. [3] offered criticisms of association studies and the reader is encouraged to weigh them against the evidence presented here. My rebuttle is that the above βindings are also consistent with reactive oxygen DNA adduct mutations’ range of cancers, defective tumor suppressor genes and Warburg effects from mitochondrial OP knockdown and antibiotic induced dysbiosis induced immune compromise. Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks https://www.heighpubs.org/jccm 167https://doi.org/10.29328/journal.jccm.1001104 IARC anomaly discussion The problem in developed countries is that use a lot of antibiotics is that infection related cancers are lower than in the Third World [cf. 7.4% versus 22.9%] showing that they are protective for these but overall reported in 2019 in Canada for example is that cancer incidence reported is 50% [37]. This suggests carcinogen and life style related cancers (see Proposition 65 list) and perhaps population of age classes contribute to the high rate. This anomaly suggests cumulative mutations and other mechanisms such as I am investigating and exposures are setting the stage for later cancer illness. That we have long insidious exposure to mutation inducing carcinogens and endocrine disruptors is conβirmed by my review of pesticide and chemical carcinogens in mothers breast milk [38]. CRC cancers increasing in Canada How safe and contributory to cancer are antibiotics? This can be addressed considerably by the experiments I propose at the end of this article. Colorectal cancers (CRC) are very informative in this story. CRC incidence increased exclusively in young adults in nine high-income countries spanning three continents, potentially signalling changes in early-life exposures that inβluence large bowel carcinogenesis [39] and a fail for antibiotics for this cancer and microbiome dysbiosis may play a pivotal role. Another intriguing possibility is inherited epigenetic markers from parental exposures. Alcohol and obesity are confounding factors for CRC etiology with interaction effects [40]. Downregulation of tumor suppressor gene TUSC3 facilitates proliferation of colon cancer CRC. Its absence or dysfunction of expression after exposure to chemicals and drugs can give a prognosis of chemicals safety [41]. Antibiotics change tissue environment to favour cancer metabolism by the warburg effect In addition, one of the antibiotics classes tested was linked to a decline in pyruvate, the feed stock for the citric acid cycle and ATP and NAD production or OP. With the loss or reduction of OP the default respiration glycolysis increases dominance. This is called the Warburg Effect which cancer cells have been shown to prefer in which they employ glycolysis instead of OP for their energy and this may result from defects in mitochondria(https://en.wikipedia.org/wiki/Warburg_ effect_(oncology)). It can be expected that this ideal environment for glycolysis favouring cancer cells will be the norm whenever and wherever mitochondria are damaged or ruptured as they are with these antibiotics tested and with common pesticides and if pyruvate is speciβically diminished. Increasing mitochondrial reproduction should reverse this process by restoring OP, replacing the Warburg effect, and that is exactly what is found [42]. This βinding is strong conβirmation of the carcinogenic effect of losing mitochondria and their function. Aerobic exercise suggests itself to me as a way to build up mitochondria and βight carcinogenesis via this mechanism. My Proposed Antibiotic Mitochondrial Carcinogenicity Mechanism AMCM Requirements for carcinogenesis contribution Induce mitochondrial malfunction, damage or rupture-YES; prevent mitochondria from faithful reproduction in quality and quantity-Probable; cause mutations and genetic material damage-YES; interfere with tumour suppressor genes-YES; create microbiome dysbiosis-YES; harm the immune system- YES; increase the Warburg effect-YES; statistically signiβicant associations-Probable. AMCM 1. Reactive oxygen linked to oxidative mutations of DNA found in many cancers and Lipid peroxide induces P53 mutations and mutated P53 no longer repairs DNA and may in fact assist cancer cells and probably the primary cause of some portion of hepatocelluar carcinomas 2. Glutathione deβiciency increases toxicity of many metabolites it normally neutralizes 3. Obstruct mitochondrial and microbiome lipid membrane integrity and mitochondrial replication leading to OP reduction and increasing microbiome dysbiosis 4. Reduction of OP and mutant P53 increase Warburg Effect favouring cancer cells glycolysis providing an advantage to cancer cells 5. Antibiotic induced microbiome dysbiosis immune compromise decreasing efβicacy of subjects cancer immune defense mechanisms Further research suggested by these studies includes testing all antibiotics for their mitochondrial impacts. Related mitochondrial stressors and potential ramifica- tions These βindings also raise the question are there pesticides with similar consequences? There are intriguing βindings in China. 9 Common pesticides tested induce morphological changes of mitochondria at low concentrations. Paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate and tebufenpyrad induced mitochondria fragmentation. Furthermore, some of them (paraquat, rotenone, chlorpyrifos, fenpyroximate and tebufenpyrad) caused a signiβicant dose-dependent decrease of intracellular ATP suggesting increased risk of Warburg syndrome because ATP is a proxy for OP integrity. Interestingly, these pesticides which induce mitochondria dysfunction also inhibit 26S Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks https://www.heighpubs.org/jccm 168https://doi.org/10.29328/journal.jccm.1001104 and 20S proteasome activity [43] which suggests to me we should be looking at antibiotics and proteasome homeostasis because of its required integrity for health. These results in turn raise the obvious question, are the consequences similar in terms of potential long term carcinogenicity? The answer is yes [44] in which they state that “Chemicals in every major functional class of pesticides including insecticides, herbicide, fungicides, and fumigants have been observed to have signiβicant associations with an array of cancer sites”. Biocide-mitochondrial effects on heart function Another interesting question. The heart muscle is full of mitochondria. Do antibiotics and pesticides affect the hearts mitochondria and if so in what way and for how long? I would expect this heart loss of OP combined with ROS and increased peroxides to lead to a condition like chronic fatigue and possibly compromised coronary function. Azithromycin induced increased deaths in patients with prior coronary issues according to study authors Wayne A. Ray, Ph.D. and C. Michael Stein, M.B., Ch.B., and Dan May 17 May 2012. John R. Giudicessi et al. 2013 [45,46] also found increased risk of sudden death from Azithromycin. Azithromycin is a macrolide which prevents bacteria from growing by interfering with their protein synthesis. How this might be linked to mitochondrial protein production needs to be examined. A UBC study found a 2.4 X increased risk of mitral valve regurgitation in βluoroquinolone users [47]. This is an area needing more research and review. FDA [48] issued a warning that some antibiotics used for URI’s and urinary infections can cause aortic rupture and prescriptions to people at risk is contraindicated. Lifetime cumulative augmentation Cumulative antibiotic for clinical treatment exposures are unwittingly augmented by chronic low level residues of other antibiotics from dietary sources like poultry, beef, farmed βish and pork and may not immediately cause a cancer but may contribute to the conditions for one to occur at a later date by facilitating entry of carcinogenic infectious agents. Other mutagens and carcinogen residues (See California Proposition 65 List), radiation, chemical and pesticide residues and immune decline with age can complete the cancer induction. Calghatgi (1973) suggests that deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l- cysteine or prevented by preferential use of bacteriostatic antibiotics. Is this sufβicient to eliminate the microbiome dysbiosis immune depression effects and does it work for all antibiotics including tetracycline which speciβically targets relatives of mitochondria in humans? This needs critical examination because of the enormous populations exposed. An evolution approach enables these extrapolations These βindings in normal mitochondria of their stress response to antibiotic biocides is consistent with their evolutionary origin from Rickettseae alpha-proteobacteria and are linked to biochemical pathways already shown linked to carcinogenesis and conβirmed in the literature. Another probably most deβinitive path to investigate the carcinogenicity of antibiotics is to run epigenetic proβiles on them to determine of they are able to turnoff genes found turned off in DNA and microRNA in cancers [49,50]. Each antibiotic and mitochondria rupturing pesticide should be put through trials to look for P53 upregulation, mutation (mutP53) and epigenetic silencing in mice and rats at ppb resolutions. Calghatgi tests should be included on all antibiotics and pesticides that rupture mitochondria at ppb resolutions as well as testing for missense mutations, characteristic of p53 mutations associated with carcinogenesis [51] and of course the CRC risk indicator assay pre and post antibiotic treatment for [8-oxodG] titre. A simple test to determine Warburg potential would be to compare pre and post antibiotic treatment intracellular ATP titre. Uncontacted Tribes with infection linked cancers might also be good controls for p53 mutations, p53 upregulations, p53 epigenetic silencings but some of them would of course have been exposed to plants that have traditional medical effects [52] and their sample size would be small. Another potential cell guardian to assess for antibiotic related mutations, epigenetic silencing is the suspected tumor suppressor trichoplein/mitostatin (TpMs) which inhibits mitofusin-2 and hence mitochondrial associated membrane formation, but is downregulated or mutated in a number of types of cancer [53]. Challange to my fundamental thesis, Wallace 2012 [54] Wallace opens with cancer needs functional mitochondria to prosper. This seems to imply disaster for my above hypothesis. However in further reading I βind his conclusions strongly supportive. My response to his work is this. How do his βindings speak to my antibiotic-mitochondrial knockdown- cancer hypothesis? The glutathione, ROS, lipid peroxide DNA mutagenicity, microbiome dysbiosis are part of my answer. He also [supportively] states “mitochondrial reactive oxygen species (ROS).......altering the activities of transcription factors such as HIF1α and FOS–JUN to change gene expression and stimulate cancer cell proliferation.” Moreover he adds “Cancer cell ROS production inactivates caveolin 1 in adjacent stromal βibroblasts. This increases mitophagy, reduces mitochondrial function and increases lactate production in these βibroblasts. Secreted stromal cell lactate then fuels cancer cell oxidative metabolism, which drives tumour growth and proliferation. This is known as the ‘reverse Warburg effect’. Its clear that one analysis needed to determine antibiotic/biocide/selected pesticide carcinogenicity is to measure the cancer cells mitochondrial ROS and lipid peroxide output in response to biocide use. I expect cancer cell mitochondria to respond the same as normal cellular mitochondria with low glutathione, increased ROS and lipid peroxide. This is an easy test. A careful read shows his work is supportive of my hypothesis. Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks https://www.heighpubs.org/jccm 169https://doi.org/10.29328/journal.jccm.1001104 Follow up research To resolve the safety of antibiotics (Abs) regarding their potential impact on mitochondrial impacts, I have arrived a number of research questions which can help steer our understanding and antibiotic futures. Independent academic institutional involvement is preferred so that vested interests don’t cloud the results. 1. How large and persistent is the glutathione decrease, ROS and lipid peroxide increase post antibiotic treatment for each antibiotic if any? 2. What effect do Abs have on future reproduction, integrity and populations of mitochondria in heart muscle. 3. Need to survey and list genetic mutations and epigenetic alteration of cancer gene expression and especially cancer gene silencing post Abs treatment in DNA and microRNA. 4. Assess dysbiosis linked impacts on immune system post Abs treatment and duration of the effect. 5. Do a full analysis of coronary function and mitochondrial health post Abs for each Abs. 6. Broad survey of Abs clastogenicity with complete description. 7. Which Abs rupture mitochondria and or cells and at what concentrations? 8. Assay 8-oxodG post Abs treatment to determine potential carcinogenicity? 9. Do any Abs impact on promotion of hepatocellular carcinoma and CRC? 10. Assay tumor suppressor epigenetic gene up-regulation, down-regulation, silencings and mutations and their loci for P53 and TUSC and TpMs. 11. Conduct a population study for Abs usage and Breast Cancer with proper controls and examine BC associated genes [55] for mutations or epigenetic silencings post Abs treatments and relationship to exposure history. 12. Assess OP and glycolysis potential of each Abs to determine potential for Warburg effect. 13. Abs history study of HPV oropharyngeal cancers in men in developed countries. 14. Abs impact on proteasome activity. 15. Assay Abs for reverse Warburg activity for H1F(alpha) and FOS-JUN which stimulate cancer cell proliferation. 16. Assay Abs treatment for caveolin 1 in adjacent stromal βibroblasts which increase mitophagy and lactate in βibroblasts driving tumor growth and proliferation. 17. Routine clinical assay for interstitial ATP titre recovery once antibiotic use is discontinued to see if the Warburg effect if initiated on application has been neutralized. I think this would clarify the scale and degree of impact of antibiotics and point to areas needing remedies. 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