The mechanisms by which metals induce cancer are currently under investigation at several levels of biological complexity. In the whole animal, cadmium has proven to be a prostatic carcinogen following oral exposure and can induce tumors of the hematopoietic systems in rats and mice from various routes. On the other hand, dietary zinc deficiency appears to cause a generalized increase in the chronic toxic and carcinogenic effects of cadmium in rats, especially in the testes and at the injection site. A remarkable non-carcinogenic chronic toxic effect of cadmium, specifically the development of atherosclerosis-like lesions in high incidence, was detected in rats. The F344 rat was found to be particularly sensitive to the carcinogenic effects of cadmium, at least at the injection site. In contrast, in the B6C3F1 mouse liver and lung, cadmium was found to be an effective anticarcinogen and was able to essentially abolish N-nitrosodiethylamine-induced hepatic and pulmonary tumors in a dose related fashion. Furthermore, in a liver cell line that undergoes spontaneous transformation, the expression of the metallothionein gene, a major part of the cellular defense mechanisms against cadmium, was markedly reduced thereby increasing the susceptibility of these cells to cadmium-induced cytolethality. In other studies concerning the metallothionein gene, it was determined that zinc pretreatment in cultured cells reduced cadmium genotoxicity by activating metallothionein gene expression.
