Genotoxic Effects in C57Bl/6J Mice Chronically Exposed to Arsenate in Drinking Water and Modulation of the Effects by Low-Selenium Diet

Abstract

In C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or 500 μg As/L, genotoxic effects in bone-marrow cells using micronucleus test and in peripheral blood leukocytes using the comet assay were determined after 3, 6 or 12 mo. To assess the modulating role of selenium in development of the effects, the animals were fed a specially prepared low-selenium diet and were supplemented with sodium selenite (200 μg Se/L) in drinking water (supplemented groups) or were without Se supplementation (nonsupplemented groups). Measurements of glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma were performed after 3, 6, and 12 mo and showed a marked decrease in values in animals in non-Se supplemented compared to Se-supplemented groups. After 3 mo of arsenic exposure in the Se-supplemented animals the level of DNA fragmentation (without Endo III and Fpg enzymes) did not differ from the control; however, increased oxidative damage of purine and pyrimidine bases was observed. In groups not supplemented with Se, an increase of DNA fragmentation was observed; however, the levels of oxidative DNA damage in these groups did not differ from the control. None of the positive effects observed in the comet assay after 3 mo was related to arsenate concentration. The levels of DNA damage after 6 and 12 mo of exposure to arsenic as well as the frequency of micronuclei after 3, 6, and 12 mo did not differ significantly between exposed and control animals, irrespective of Se supplementation status.

These investigations were supported by grant 662/PO5/2001/21 from the Polish State Committee for Scientific Research. The authors thank Barbara Pawlak, Mariola Włodarek, and Barbara Kołodziejczak for their excellent technical assistance.