Recent advances in chromium genotoxicity†

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Abstract
More than 350 short‐term genotoxicity tests have been performed up to date with Cr compounds, the more recent of which deal with the following aspects: (1) New tests have been developed to evaluate the mutagenicity of Cr, by the introduction of cell strains particularly sensitive to Cr(VI) mutagenicity, and the determination of particular conditions allowing to detect the genetic activity also of Cr(III). (2) Interactions of Cr(VI) and Cr(III) with purified nitrogen bases, polynucleotides, DNA, chromatin, nuclei and whole cells, have led to the identification of specific Cr(III)‐DNA adducts, structural alterations of the genetic material, and effects on the DNA‐repair functions, which can vary in different cell types and tissues. (3) The metabolism of Cr(VI) in mitochondrial, microsomal and soluble cell fractions has been related to inactivation mechanisms, some of which are inducible by Cr(VI) itself. Specific cell components able to reduce Cr(VI) to Cr(III), possibly via genetically active intermediate oxidation forms, have been identified. (4) Cytotoxic effects of Cr(VI) and Cr(III) have been detected in different cell systems, and some of them, such as the interferences with cell proliferation kinetics and DNA replication cycle, the effects on nucleic acid synthesis, and the embryotoxic effects, may be related to genotoxic mechanisms. (5) Interactions of Cr(VI) with other genotoxic agents have been pointed out, those with some environmentally relevant contaminants (such as nitrilotriacetic acid) being of particular interest. The already proposed mechanisms of Cr genotoxicity and the correlations between the mutagenic and carcinogenic activity of Cr are reviewed on the basis of the present data.