Abstract
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. Till now no genomic hot spot has been identified which is frequently hypermethylated or hypomethylated in persons chronically exposed to environmental arsenic. In the present work, we have identified one hypermethylated sequence by methyl-sensitive arbitrarily primed polymerase chain reaction in the peripheral blood leukocyte DNA of chronically arsenic exposed persons with and without arsenic induced skin cancer. The sequence is from GMDS gene responsible for fucose metabolism. Southern hybridization of the sequence to the amplification products of methyl sensitive restriction enzyme digested genome of persons exposed to different doses of arsenic indicated that methylation increased in a dose dependent manner.
Highlights
According to (International agency for research on cancer 1997) and National Research Council (NRC 1999) arsenic is an important environmental toxicant and carcinogen
The hypothesis that arsenic perturbs DNA methylation has been tested successfully on tissue culture system (Mass and Wang 1997), and later we demonstrated hypermethylation of the promoter region of p53 and p16 genes in DNA extracted from peripheral blood leucocytes of persons exposed to different doses of arsenic (Chanda et al 2006)
The sequence is analysed by bioinformatic tools (NCBI BLAST) to indicate that the fragment is situated in the human GDP mannose 4–6 dehydratase gene (GMDS gene). Southern hybridization of this fragment to amplified products from methyl sensitive restriction enzyme digested genomic DNA of persons exposed to arsenic in drinking water indicated that the sequence is hypermethylated
Summary
According to (International agency for research on cancer 1997) and National Research Council (NRC 1999) arsenic is an important environmental toxicant and carcinogen. The hypothesis that arsenic perturbs DNA methylation has been tested successfully on tissue culture system (Mass and Wang 1997), and later we demonstrated hypermethylation of the promoter region of p53 and p16 genes in DNA extracted from peripheral blood leucocytes of persons exposed to different doses of arsenic (Chanda et al 2006). The sequence is analysed by bioinformatic tools (NCBI BLAST) to indicate that the fragment is situated in the human GDP mannose 4–6 dehydratase gene (GMDS gene). Southern hybridization of this fragment to amplified products from methyl sensitive restriction enzyme digested genomic DNA of persons exposed to arsenic in drinking water indicated that the sequence is hypermethylated. Though have been found here in small proportion this hypermethylated fragment may be act as a potential target (probe) for detecting aberrant methylation in chronic high level of arsenic exposure
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