Mutagenesis of AS52 cells by low concentrations of lead(II) and mercury(II)

Little is known at the molecular level concerning the genotoxic effects following the acute exposure of eukaryotic cells to low concentrations of lead (II) or mercury (II). There have been conflicting reports concerning the mutagenic potential of these heavy metals, and there have not been any studies performed to determine the molecular mechanism(s) by which these metals are mutagenic. The Chinese hamster ovary cell line, AS52, contains a stably integrated single functional copy of the Escherichia coli xanthine-guanine phosphoribosyltransferase (gpt) gene. Mutations in the gpt gene confer resistance to 6-thioguanine (TG). There was little effect on viability, as measured by relative cloning efficiency, of AS52 cells exposed to lead (II) or mercury (II) up to concentrations of 0.5 microM and 0.3 microM, respectively. However, higher concentrations of the metals caused a significant increase in cell death. There was also a dose-dependent increase in the isolation of mutants resistant to TG in treated cells when compared to non-treated controls. Concentrations of the metals as low as 0.1 microM caused a significant increase in the number of mutants resistant to TG when compared to the number of spontaneous mutants obtained in nontreated controls. While the molecular mechanism(s) by which lead and mercury (II) are genotoxic is unknown, the results of this study demonstrate that low concentrations of lead (II) and mercury (II) are mutagenic in eukaryotic cells.