Effect of chronic dietary zinc deficiency on cadmium toxicity and carcinogenesis in the male Wistar [Hsd: (WI)BR] rat

Abstract

Though it is known that excess zinc will prevent cadmium carcinogenesis, the impact of zinc deficiency on cadmium carcinogenesis has not been defined. This study assessed the effect of dietary zinc deficiency on the carcinogenic potential of cadmium in rats. Groups ( n = 28 each) of male Wistar [Hsd: (WI)BR] rats were fed diets adequate (60 ppm) or deficient (7 ppm) in zinc and received a single sc dose of cadmium (5, 10, or 30 μmol Cd/kg). Lesions were assessed over the next 92 weeks. All cadmium doses increased the incidence of testicular interstitial cell tumors. The incidence of cadmium-induced testicular tumors was unaffected by dietary zinc status. However, when multiplicity of testicular lesions was considered, zinc-deficient diets markedly increased the number of testicular interstitial cell adenomas generated by cadmium exposure while significantly reducing the number of preneoplastic lesions (interstitial cell hyperplasias). The combined total number of neoplastic and preneoplastic lesions of the testes was independent of zinc status clearly indicating a shift from hyperplasia to neoplasia within the testes of zinc-deficient rats. The highest cadmium dose (30 μmol/kg) increased injection site sarcomas in zinc-deficient rats (7 tumors/27 rats at risk) but not zinc-adequate rats ( 3 26 ) when compared to control ( 0 49 ). Chronic progressive renal nephropathy was accelerated by cadmium in zinc-deficient rats. Results indicate that dietary zinc deficiency enhances carcinogenic response at the injection site of cadmium, promotes the neoplastic progression of cadmium-induced testicular lesions, and enhances chronic progressive nephropathy. Thus, dietary zinc deficiency appears to cause a generalized increase in the chronic toxic effects of cadmium.