Human GMDS gene fragment hypermethylation in chronic high level of arsenic exposure with and without arsenic induced cancer.

Arsenic, though a poor mutagen, is an accepted environmental carcinogen. Perturbation of DNA methylation pattern leading to aberrant gene expression has been hypothesized as the mechanism for arsenic induced carcinogenesis. We had earlier demonstrated the hypermethylation of promoter region of p53 and p16 genes in persons exposed to different doses of arsenic.

Arsenic exposure induces genomic hypermethylation.

Gene-specific hypermethylation has previously been detected in Arsenic exposed persons. To monitor the level of whole genome methylation in persons exposed to different levels of Arsenic via drinking water, DNA was extracted from peripheral blood mononuclear cells of 64 persons. Uptake of methyl group from (3)H labeled S-Adenosyl Methionine after incubation of DNA with SssI methylase was measured.

DNA hypermethylation of promoter of gene p53 and p16 in arsenic-exposed people with and without malignancy.

Chronic arsenic exposure is known to produce arsenicosis and cancer. To ascertain whether perturbation of methylation plays a role in such carcinogenesis, the degree of methylation of p53 and p16 gene in DNA obtained from blood samples of people chronically exposed to arsenic and skin cancer subjects was studied. Methylation-specific restriction endonuclease digestion followed by polymerase chain reaction (PCR) of gene p53 and bisulfite treatment followed by methylation-sensitive PCR of gene p16 have been carried out to analyze the methylation status of the samples studied.