Inhibition of potassium dichromate mutagenicity by todralazine

Abstract

Todralazine, an antihypertensive drug of the hydrazinophthalazine group, markedly decreased the mutagenic activity of potassium dichromate in standard bacterial tests. At the highest todralazine dose tested inhibition of potassium dichromate mutagenic activity by ~ 90% in the Ames test and up to 100% (complete) inhibition in the Bacillus subtilis rec- assay was observed. Spectrophotometric analyses proved that todralazine induced reduction of Cr(VI) to Cr(III) and complexation of Cr(III) ions. These spectrephotometric results may be a presumptive explanation of the observed mutagenic activity decrease, as it is known that Cr(III) is poorly transported across cell membranes and therefore is not mutagenic to bacterial cells. We perceive our experiments as an example of attempts which should lead to an effective reduction in chromium genotoxic and carcinogenic activity in exposed individuals.