Bisulfite induced P53 gene mutation of G:C--->A:T Probably leading to lung cancer Partial Explanation of one Cancer Common in pulp industry? 18 Jan 2013. Jorma Jyrkkanen. jormabio@hotmail.com

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/. Abstract Exogenous H2S in the bisulfite ionic form HSO3- produced by T4RII Phage is a very likely source of this small cell and non-small cell lung carcinogen augmenting endogenous sources and contributing to the statistical incidence of lung cancers in Pulp Mill Districts by critical mutagenesis of tumor suppressor genes. Key Words cancer genes, cancers, carcinogens, carcinogens mutagens teratogens gender, health, jorma jyrkkanen, mutagens carcinogens genderbenders terat, pulp mills Discussion 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. Recent Findings Hydrogen sulfide (H2S) has been frequently implicated in tumor progression. However, the exact regulation mechanism of H2S in human non-small cell lung cancer (NSCLC) has not been fully elucidated. Here, analysis of NSCLC biopsies and adjacent non-tumor tissues revealed selectively high levels of endogenous H2S-producing enzymes, cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST). Similarly, quantitative real-time PCR (qRT-PCR) and western blot results showed that NSCLC cell lines (A549, 95D) expressed higher levels of CBS, CSE and MPST in mRNA and enzyme proteins, respectively. Moreover, NSCLC cell lines produced more H2S than did the normal lung epithelial cell line BEAS-2B. H2S was further detected to induce NSCLC migration and invasion, as well as the epithelial mesenchymal transition (EMT) process. Small interfering RNA (siRNA) silencing of CBS or CSE activity reduced proliferation and metastasis potential of tumor cells. In addition, H2S modulated hypoxia-inducible factor-1α (HIF-1α) to stimulate vascular endothelial growth factor (VEGF) expression, which contributes to tumor angiogenesis. Treatment of nude mice with pharmacological inhibition of CBS or CSE activity decreased xenograft growth and suppressed angiogenesis. Collectively, these results indicate H2S plays an important part in NSCLC growth and angiogenesis by HIF-1α activation, which potentially provide new insight in therapeutic strategies. Wang M, Yan J, Cao X, Hua P, Li Z. Hydrogen sulfide modulates epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via HIF-1α activation. Biochem Pharmacol. 2020 Feb;172:113775. doi: 10.1016/j.bcp.2019.113775. Epub 2019 Dec 20. PMID: 31870768 Jorma Jyrkkanen Original 1991. Tags: cancer genes, cancers, carcinogens, carcinogens mutagens teratogens gender, health, jorma jyrkkanen, mutagens carcinogens genderbenders terat, pulp mills