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.
Ochi
T
T
Department of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Takahashi
K
K
Ohsawa
M
M
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D019256:Cadmium Chloride; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D009153:Mutagens; D009154:Mutation; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D011490:Protein Disulfide Reductase (Glutathione); D013482:Superoxide Dismutase / Q000378:metabolism
D054477:Glutaredoxins; D009153:Mutagens; D002104:Cadmium; D002084:Butylated Hydroxytoluene; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D011490:Protein Disulfide Reductase (Glutathione); D005978:Glutathione; D019256:Cadmium Chloride