The influence of antioxidants on the genotoxicity of chemical mutagens detected with the SOS chromotest

293 SCEs, whereas the blocking of H U concentrations had no comparable effect. The effect of H U on the frequencies of SCEs therefore depends on the treatment protocol. Exposure of cells to H U before BrdU labeling does not cause elevated SCE frequencies in second-division mitoses. SCE induction is only found in cells which have replicated in the presence of BrdU and HU, or which have replicated BrdU-substituted D N A in the presence of HU. The treatment conditions leading to strong SCE induction due to delay of replication did not increase the frequencies of H P R T mutants. It is discussed whether the disturbance of D N A synthesis by H U is not sufficient to cause mutations in Chinese hamster cells or whether a delayed toxic effect leads to a false negative result in the H P R T test.

39 v o n d e r Hude, W., J. Potenberg, R. Kahl, C. Behm and A. Basler, Max von Pettenkofer-Institut des Bundesgesundheitsamtes, Postfach 33 00 13, D1000 Berlin 33 (F.R.G.) The influence of antioxidants on the genotoxicity of chemical mutagens detected with the S O S chromotest Some antioxidants are known to inhibit the tumor-inducing potency of chemical carcinogens. An enhancement, on the other hand, has also been observed. Furthermore, the non-genotoxic antioxidants BHT and BHA caused cancer in long-term animal studies. Moreover, a decrease as well as an enhancement of mutagenicity of chemical mutagens by antioxidants has been reported. In the

present experiments the SOS chromotest was performed to reevaluate the genotoxicity of antioxidants and to elucidate the reported contradictory effects of antioxidants on the genotoxicity of chemical mutagens. The direct-acting mutagens hydroxyurea and hydrogen peroxide increased the SOS induction factor dose dependently. The promutagens benzo[a ]pyrene and 2-aminoanthracene induced the SOS function in the presence of a metabolizing system ($9 mix). All tested synthetic antioxidants, butylated hydroxytoluene, butylated hydroxyanisole, ethoxyquin, propyl gallate, octyl gallate and dodecyl gallate and the natural antioxidants, ascorbic acid and a-tocopherol, as well as the cofactors, glutathione and FMN, were not genotoxic. These compounds were tested in combination with the above-mentioned mutagens. Different concentrations of the antioxidants were combined with different concentrations of the mutagens. Different antioxidant-mediated effects were detected. Some antioxidants had an antimutagenic effect when combined with some mutagens, whereas a synergistic effect of these antioxidants resulted in combination with other mutagens. Furthermore, even a biphasic response of antioxidant action was detected: In some combinations an increase of the induction factor was observed in the lower antioxidant concentration range whereas inhibition occurred at high concentrations of mutagens and antioxidants. This demonstrates that it is necessary to perform the test over a sufficient range of mutagen and antioxidant concentrations to evaluate the different influence of antioxidants on the genotoxicity of chemical mutagens.