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DIETARY FOLATE DEFICIENCY ENHANCES ARSENIC-INDUCED MICRONUCLEUS FORMATION IN MICE
Citation:
McDorman, E., B W. Collins, AND J W. Allen. DIETARY FOLATE DEFICIENCY ENHANCES ARSENIC-INDUCED MICRONUCLEUS FORMATION IN MICE. Presented at 2001 Environmental Mutagen Society 32nd Annual Mtg, San Diego, CA, March 16-21, 2001.
Description:
Dietary folate deficiency enhances arsenic-induced micronucleus formation in mice.
Folate deficiency increases background levels ofDNA damage and can enhance the mutagenicity of chemical agents. Duplicate experiments were performed to investigate the effect of dietary folate deficiency on arsenic induction of micronuclei (MN) in peripheral blood. Male C57BI/6J mice were fed folate-deficient (FD) or folate-replete (FR) diets for 7 weeks. During week 7, mice on each diet (n = 5 per group) were given 4 consecutive daily doses of sodium arsenite (0,2.5,5, or 10 mg/kg) or acrylamide (positive control; 50 mg/kg) via oral gavage. In both experiments, the FD diet produced an approximate 50% depletion of red blood cell folate. Two-way ANOVA revealed a statistically significant interaction (p < 0.05) bet\veen folate status and arsenic dose in micronucleated polychromatic erythrocytes (PCEs) in both experiments. Increases in MN-PCE levels observed were approximately twice as high in FD mice as compared to FR mice at 10 mg/kg; the effect of arsenic in combination with folate deficiency was greater than the sum of the effects of arsenic and folate deficiency alone. No interaction was observed in micronucleated normochromatic erythrocytes. Very few MN from either control or treated animals in either experiment revealed kinetochore immunostaining, indicating that MN were derived from chromosome breakage rather than from whole chromosome loss. These results indicate that folate deficien~y enhances arsenic-induced clastogenesis at high doses. Because arsenic and folate deficiency both interfere with DNA repair, alterations in repair processes may contribute to the high MN levels observed. (This research was supported in part by EPA Training Agreement CT827206 to EWM.
This abstract does not necessarily represent US EPA policy.