Coordination chemistry and the carcinogenicity and mutagenicity of chromium(VI)

Abstract

Chromate is a known carcinogen, it is only in recent years that the molecular mechanisms by which this toxicity may be expressed have been investigated. The toxicity of chromate may be mediated by the reaction of chromium(VI) with glutathione (GSH) to generate relatively stable chromium(V) complexes and other more reactive intermediates. The conditions favouring the formation of such complexes have been studied. Reactive intermediates generated during the reduction of chromate by GSH include thionyl radicals and at least two relatively stable chromium(V) species (g -1.996 and g -.986). Mixtures of chromium(VI) and glutathione and a chromium(V) complex of glutathione, which we have isolated from the reaction (g = 1.996), are capable of causing strand breaks in bacteriophage PM2 DNA. In contrast a chromium(III) complex of GSSG, one of the final products of the reaction between GSH and chromium(VI), does not damage DNA in closed circle assays. These observations support the suggestion that reactive intermediates generated during the reduction of chromium(VI) provide one route by which the genotoxicity of chromate may be expressed.