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EFFECTS OF DIETARY FOLATE ON ARSENIC-INDUCED GENE EXPRESSION IN MICE
Citation:
Thai, S. F., J A. Barnes, E. McDorman, J C. Fuscoe, AND J W. Allen. EFFECTS OF DIETARY FOLATE ON ARSENIC-INDUCED GENE EXPRESSION IN MICE. Presented at Environmental Mutagen Society, Miami Beach, FL, May 10 - 14, 2003.
Description:
Effects of Dietary Folate on Arsenic-induced Gene Expression in Mice
Arsenic, a drinking water contaminant, is a known carcinogen. Human exposure to inorganic arsenic has been linked to tumors of skin, bladder, lung, and to a lesser extent, kidney and liver. Dietary folate is necessary for regeneration of S-adenosylmethionine used in arsenic metabolism and maintenance of normal DNA methylation, and for DNA synthesis and repair. Several recent studies in mice have indicated that folate can protect against arsenic toxicity/genotoxicity. In the present studies conducted in mice, we have evaluated the effects of dietary folate to modulate arsenic-induced alterations in gene expression. Male C57Bl/6J mice were fed folate-deficient or folate-sufficient diets for 7 weeks. During the last four days, they were treated with consecutive daily doses of sodium arsenite (10 mg/kg), or water (control), via oral gavage. With Northern blot analysis of replicate liver RNA samples from each of three mice/experimental group, the cytochrome P450 genes CYP2A4/5 and CYP2C29 consistently showed arsenic-induced increases in levels of expression over control (e.g., > or = to 10-fold for CYP2A4/5) in folate-deficient mice. However, arsenic-induction levels for these genes were uniformly lower in mice fed the folate-replete diet. That dietary folate reduces arsenic-induced CYP2A4/5 expression levels is of interest in relation to previously reported involvement of CYP2A5 overexpression in liver tumors of mice. Studies are ongoing to distinguish between CYP 2A4 and 2A5, and determine possible mechanisms of tumor induction involving this pathway. (This abstract does not necessarily reflect EPA policy)