Heterogeneity of the DNA damage provoked by antimony and arsenic.

Abstract

Data on the mechanism of antimony genotoxicity is scarce. Arsenic and antimony are proposed to share some toxicological features. Thus comparative and combined experiments with As(III) and Sb(III) were performed to gain a deeper knowledge of the mechanism of antimony genotoxicity. Trivalent arsenic proved to be five times more cytotoxic and one order of magnitude more potent in induction of micronuclei in human lymphocytes in vitro than was antimony. Significantly increased micronucleus frequencies were achieved with As(III) at a dose of 0.5 microM and with Sb(III) at a dose of 5 microM. Neither the number of micronuclei induced by As(III) nor by Sb(III) could be suppressed by co-incubation with superoxide dismutase or catalase. This suggests that induction of oxidative stress may not be a crucial step in the mechanism of DNA damage induction by arsenic and antimony. The combined genotoxicity in micronucleus test co-incubation experiments with arsenic and antimony seemed best described by simple additivity. In the single cell gel test with human lymphocytes a significant induction of DNA damage was observed with 0.01 microM As(III) and 5 microM Sb(III). In contrast to Sb(III), As(III) proved to be a very potent inducer of DNA-protein crosslinks. It may be that Sb(III) as well as As(III) causes DNA damage by inhibition of enzymes involved in DNA repair. Further investigations will have to identify the relevant sites of action.