THE GENETIC TOXICOLOGY OF COBALT

Genetic and related effects of cobalt compounds are reviewed and discussed with respect to mechanisms. In prokaryotic assays, Co(II) salts generally are nonmutagenic. In Saccharomyces cerevisiae, CoCl2 is mutagenic to mitochondrial genes and weakly mutagenic or nonmutagenic to chromosomal genes. In plants, Co(II) salts induced gene mutations and chromosomal aberrations. In mammalian cells in vitro, Co(II) compounds caused DNA strand breaks, sister-chromatid exchanges and aneuploidy, but not chromosomal aberrations. In two cell lines, CoCl2 was weakly mutagenic. Interestingly, the poorly soluble compound CoS caused DNA strand breaks and morphological transformation of mammalian cell lines. In contrast to its weak clastogenic and mutagenic properties, cobalt(II) exerts pronounced antimutagenicity in bacteria and mostly comutagenic effects in mammalian cells. In Escherichia coli CoCl2 lowered the frequency of mutations induced by MNNG, uv or X rays. In Chinese hamster V79 cells, CoCl2 enhanced the mutagenicity and clastogenicity of uv light but not of γ rays. Regarding direct genotoxic mechanisms, Co(II) induces the formation of reactive oxygen species when combined with hydrogen peroxide in cell-free systems. At high (i.e., millimolar) concentrations, Co(II) also decreases the fidelity of DNA synthesis. Regarding anti- and comutagenic mechanisms, evidence for the interference of Co(II) with DNA repair processes is discussed. These mechanisms are regarded as relevant for the risk assessment of human exposure to cobalt in combination with other agents. © 1992.