Micronucleus formation in human lymphocytes and in the metabolically competent human hepatoma cell line Hep-G2: results with 15 naturally occurring substances.

To examine the concordance of two metabolizing systems for use in genotoxocity testing with the micronucleus test, 15 naturally occurring substances (arecoline, the plant extract aristolochic acid, beta-asarone, benzyl acetate, coumarin, emodine, isatidine dihydrate, monocrotaline, psoralen, reserpine, retrorsine, safrole, sanguinarine chloride, tannin and thiourea) were tested for their genotoxicity in the cytokinesis-block micronucleus test in vitro with human lymphocytes and in the presence and the absence of an exogenous metabolizing system from rat liver S9-mix and the metabolically competent human hepatoma cell line Hep-G2. Arecoline, the plant extract aristolochic acid, psoralen and tannin caused a significant increase in the number of micronuclei in human lymphocytes in the presence and the absence of an exogenous metabolising system from rat liver S9-mix and the metabolically competent human hepatoma cell line Hep-G2. A significant increase in the number of micronuclei with beta-asarone, coumarin, monocrotaline and retrorsine could be detected in the presence of S9-mix and the cell line Hep-G2. Benzyl acetate, emodine, isatidine dihydrate, reserpine, safrole, sanguinarine chloride and thiourea did not reveal any micronucleus inducing activity in either human lymphocytes or in Hep-G2. In addition to the other Hep-G2 results in the literature, this human hepatoma cell line could have a useful potential in the in vitro micronucleus test.

Arsenic(III), but not antimony(III), induces DNA-protein crosslinks.

Antimony compounds are supposed to resemble to arsenicals in some toxicological features. Comparative investigations with antimony and arsenic were performed to collect data on the genotoxicity of antimony, on which the knowledge is scarce. In comparison to trivalent arsenic, trivalent antimony proved to be five times less cytotoxic in the neutral red assay and one order of magnitude less genotoxic in the cytokinesis-block micronucleus test using V79 Chinese hamster cells. The data obtained in the comet assay showed that the As(III)-mediated generation of DNA-protein crosslinks and DNA strand lesions seem to be two independent processes. In contrast, Sb(III) induced DNA strand lesions but not DNA-protein crosslinks. Further studies will have to investigate whether the genotoxicity of Sb(III) is mediated by an inhibition of DNA repair as it seems to be the case for As(III).