HETEROGENEITY OF THE DNA-DAMAGE PROVOKED BY ANTIMONY AND ARSENIC

Data on the mechanism of antimony genotoxicity is scarce. Arsenic and antimony are proposed to share some toxicological features. Thus compa rative and combined experiments with As(III) and Sb(III) were performe d to gain a deeper knowledge of the mechanism of antimony genotoxicity . Trivalent arsenic proved to be five times more cytotoxic and one ord er of magnitude more potent in induction of micronuclei in human lymph ocytes in vitro than was antimony. Significantly increased micronucleu s frequencies were achieved with As(III) at a dose of 0.5 mu M and wit h Sb(III) at a dose of 5 mu M. Neither the number of micronuclei induc ed by As(III) nor by Sb(III) could be suppressed by co-incubation with superoxide dismutase or catalase, This suggests that induction of oxi dative stress may not be a crucial step in the mechanism of DNA damage induction by arsenic and antimony. The combined genotoxicity in micro nucleus test co-incubation experiments ,vith arsenic and antimony seem ed best described by simple additivity. In the single cell gel test wi th human lymphocytes a significant induction of DNA damage was observe d with 0.01 mu M As(III) and 5 mu M Sb(III). In contrast to Sb(III), A s(III) proved to be a very potent inducer of DNA-protein crosslinks. I t may be that Sb(III) as well as As(III) causes DNA damage by inhibiti on of enzymes involved in DNA repair. Further investigations will have to identify the relevant sites of action.