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ARSENITE EXPOSURE CAUSES BOTH HYPOMETHYLATION AND HYPERMETHYLATION IN HUMAN CELL LINES IN CULTURE AT LOW CONCENTRATIONS
Citation:
Zhong, C. X., L. Wang, AND M J. Mass. ARSENITE EXPOSURE CAUSES BOTH HYPOMETHYLATION AND HYPERMETHYLATION IN HUMAN CELL LINES IN CULTURE AT LOW CONCENTRATIONS. WR Chappell,CO Abernathy and RL Calderon (ed.), Arsenic Exposure and Health Effects IV , (2001).
Description:
We and others have hypothesized that a mechanism of arsenic carcinogenesis could involve alteration of DNA methylation since this process utilizes a methyltransferase and consumes S-adenosylmethionine (SAM) as the methyl donor. We analyzed differentially methylated regions of genomic DNA from human lung A549 cells and three human kidney cell lines (UOK cell lines) observed after arsenite treatment using methylation-sensitive arbitrarily-primed PCR (MS-APPCR). Relative to untreated controls, 6 DNA fragments identified by MS-APPCR were hypermethylated and 2 were hypomethylated in DNA from these lung and kidney cell lines. Two of the DNA fragmnets contained repeat sequences of mammalian apparent LTR retrotransposons (MaLRs), and 5 were identified to be promoter-like sequences. DNA methylation alterations were manifested at low nanomolar concentrations in some cell lines. Both mRNA for DNA MTase and DNA MTase activity increased in cells exposed to arsenite over a 2-week period. Our results show the occurrence of both hypermethylation and hypomethylation of DNA that coexist during exposure to arsenite. The results, in total, could support the existence of a state of methylation imbalence (hypo- and hypermethylation) that could conceivably disrupt gene expression in arsenic exposed cells in vitro.