Evaluation of the mechanisms of todralazine effect on mutagenicity of benzo(a)pyrene.

We have previously described that todralazine markedly decreased mutagenicity of several indirect- and direct-acting mutagens. In this paper we report the results of experiments conducted in order to evaluate the involvement of desmutagenic and bio-antimutagenic activities in the observed antimutagenic effect of todralazine. The results of the Ames test suggest a bio-antimutagenic, and not desmutagenic effect of todralazine. The separation of B(a)P and their derivatives by thin layer chromatography, performed after in vitro incubation of this promutagen with S9 fraction and todralazine revealed almost complete decline of B(a)P derived products in the presence of todralazine. The results indicate that the observed antimutagenic effect of todralazine on B(a)P mutagenicity is bio-antimutagenic rather than desmutagenic in their nature.