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METHYLATION OF SODIUM ARSENITE BY VARIOUS MAMMALIAN CELLS
Citation:
Sharma, R, A D. Kligerman, AND M J. Mass. METHYLATION OF SODIUM ARSENITE BY VARIOUS MAMMALIAN CELLS. Presented at 32nd Annual EMS 2001: A Science Odyssey, San Diego, CA, March 16-21, 2001.
Description:
Methylation of Sodium Arsenite by various Mammalian Cells
Methylation of arsenite (As 3-1) is thought to play an important role in the carcinogenicity of arsenic. AIM: I. Characterization of methylation of arsenite in primary rodent and transformed human cell lines. 2. Enhancement of arsenite methyltransferase (AMTase) activity, by a hypomethylating agent, 5-aza-2'-deoxycytidine (aza-dC).METHODS:. Transformed human cell lines originating from liver (HepG2), lung [non-small cell lung cancer, A549; small cell lung cancer, H82], kidney, UOKl21 and UOKI23, testis, CRL-1973 and primary lymphocytes of human, guinea pig, mouse and rat were used for differential dose-dependent methylation of arsenite. Cells were exposed to various concentrations of 73 As-sodium arsenite for 48 hrs. Cell and media fractions were analyzed for inorganic As (III), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Pretreatment with aza-dC was performed with HepG2 cells for 48
hoursr before assessing methylation of arsenite. RESULTS : Both primary and transformed cells methylated arsenite to MMA and DMA differently. DMA (though not MMA) increased linearly at low arsenite concentrations, but DMA decreased and MMA increased at higher arsenite concentrations. Methylation capacity based on DMA formation in transformed cells was ordered: testis> liver> kidney >lung; in primary lymphocytes: rat> guinea pig> mouse> human. Pretreatment with aza-dC increased DMA formation 2-fold. CONCLUSION: Methylation of arsenite was tissue-specific in both primary and transformed cells. Aza-dC increased the methylation of arsenite possibly by hypomethylating DNA thereby derepressing the expression of AMTase.
This is an abstract of a proposed presentation and does not represent US EP A policy.