Indirect evidence for the induction of a prooxidant state by cadmium chloride in cultured mammalian cells and a possible mechanism for the induction.

The effects of scavengers of active oxygen species on cadmium chloride (CdCl2)-induced inhibition of cell growth and DNA synthesis and on the metal-induced clastogenesis were investigated to evaluate whether cadmium could induce a prooxidant state in cultured Chinese hamster V79 cells. Inhibition by CdCl2 of cell growth and [3H]thymidine incorporation into the acid-insoluble fraction of cells and the metal-induced clastogenesis were suppressed in part by the presence of the diffusible radical scavenger, butylated hydroxytoluene (BHT). The action of BHT was concentration-dependent and did not affect the intracellular level of cadmium. D-Mannitol, a hydroxyl radical scavenger, also significantly suppressed Cd-induced inhibition of cell growth and [3H]thymidine incorporation. Catalase was marginally suppressive on Cd-induced inhibition of cell growth. These results suggest that cadmium can induce a prooxidant state in cultured mammalian cells. The mechanism by which cadmium induces a prooxidant state was investigated by measuring the effect of cadmium on those enzymes which constitute a cellular defense against active oxygen and on the level of the intracellular antioxidant, glutathione (GSH). 2-h treatments with CdCl2 over a concentration range of 2-10 X 10(-5) M did not influence superoxide dismutase, catalase, GSH peroxidase or GSSG reductase. In contrast, the level of glutathione was decreased to approximately 40% by treatment with 2 X 10(-5) M cadmium. The decrease in glutathione level may be responsible for a role by active oxygen in Cd-induced inhibition of cell growth and DNA synthesis and the metal-induced clastogenesis.