DNA Damage by Mercury Compounds: An Overview

Abstract

AB - Studies on the mechanisms by which mercury (7439976) induces DNA damage were reviewed. New data were presented on the effects of methyl-mercury-chloride (115093) on DNA in cultured fibroblasts, as well as in cultured nerve cells. The most abundant DNA lesions induced by mercury in intact cultured cells were strand breaks. The appearance of DNA strand breaks correlated with the threshold of mercury-chloride (7487947) cytotoxicity. Methyl-mercury chloride and mercury-chloride both produce DNA strand breaks in cells. As these breaks are not repaired, the authors suggest these may be of significance in producing cell death. Some data suggested that there may be a dose at which mercury induces repairable stand breaks. These results suggested the possibility that at certain optimal relatively low concentrations, which may be hard to define, there may be some mutagenic and carcinogenic effects from this metal. Mercury binds tightly to the DNA and no agent was found that could dissociate the two. However, on degradation of the DNA, mercury was released from its binding sites, suggesting that mercury may be binding at the hydrogen binding sites of DNA and that the binding depends on the polynucleotide structure of the DNA. The more potent effects of methyl-mercury-chloride over mercury-chloride on the nerve cells, compared to fibroblasts, were of interest as the strand breaks follow the cytotoxic response, suggesting that strand breaks are involved in the cytotoxicity of methylmercury-chloride as well as mercury-chloride. The authors conclude that DNA strand breaks induced by methylmercury-chloride in nerve cells may be important in the ensuing cytotoxic response, but that the nerve cell is more sensitive than other cells for other reasons, such as uptake.