Chronic Arsenic Exposure Induced DNMT and MBD2 over expression associated with local DNA hypermethylation in people of West Bengal, India.

Abstract: DNMT and MBD2 gene is associated with aberrant and maintenance methylation of genes. MBD2 bind with methylated CpG island while DNMT causes addition of methyl groups to the cytosines. Both of the genes are reported to be associated with epigenetic modification in cancer promotion. To explore the role of DNMT and demethylase MBD2 in chronic arsenic exposure we have analyzed the expression profile of DNMT genes and MBD2 gene. The aim of this study is to focus the effect of arsenic induced changes in genes with special reference to epigenetic modifications. Arsenic causes local aberrant DNA methylation which is reflected in this study. We have identified one hypermethylated fragment of gene from homeobox gene and one in RASSF1A gene promoter region by methyl-sensitive arbitrarily primed polymerase chain reaction from the peripheral blood leukocyte DNA of arsenic exposed persons. Degree of promoter methylation has been studied in arsenic exposed and unexposed persons. Homeobox gene is essential for developmental processes and morphogenesis with development of ectodermal appendages, whereas RASS1A is a tumor suppressor gene which controls cell cycle. Both the Homeobox gene and RASSF1A gene hypermethylation is associated with altered expression of DNMT1, DNMT 3 and MBD2 gene.