Induction of 6-thioguanine-resistant mutants and single-strand scission of DNA by cadmium chloride in cultured Chinese hamster cells

Abstract

Inducibility of 6-thioguanine-resistant (6TG r) mutants and single-strand scission of DNA by cadmium chloride (CdCl 2) was investigated in cultured Chinese hamster V79 cells. Frequency of 6TG r mutants increased concentration dependently by 24-h treatment with CdCl 2 up to 3 × 10 −6 M but decreased beyond 3 × 10 −6 M. Mutagenic potency of cadmium in the absence of S9 was about half that of benzo[ a]pyrene in the presence of S9 at equitoxic concentrations. Treatment of the cultured cells with cadmium after benzo[ a]pyrene treatment was not synergistic but additive to the mutagenicity of benzo[ a]pyrene. Single-strand scission of DNA by alkaline elution techniques was observed in the cells treated with CdCl 2 for 2 h in a concentration-dependent manner. The single-strand scission by cadmium was detected only in combination with proteinase K digestion of the cell lysates, indicating formation of DNA-protein cross-linking by the metal. These biological and biochemical findings indicate that cadmium is mutagenic in mammalian cells, and its mutagenic effect seems to be accompanied by single-strand scission of DNA.