Mechanism of cadmium-induced rat testicular cancer.

Abstract

In order to clarify the mechanism of cadmium (Cd)-induced rat testicular cancer, cadmium (Cd) contents in the liver, kidney and testis and in hepatic, renal and testicular Leydig's cell nuclei after exposure to noncarcinogenic dose (3.87 μmol/kg, once, s.c.) or carcinogenic dose (30μmol/kg, once, s.c.) of CdCl2 were asessed. Uptake and cytotoxicity of Cd and DNA damage by the metal in hepatocytes, Sertoli's cells and Leyding's cells were also assessed. Administration of carcinogenic dose of CdCl2 to rats caused severe testicular damage as reflected by a remarkable rise in calcium content, discoloration and atrophy of the organ. In the rats given carcinogenic dose of CdCl2, when Cd contents in the testis and testicular Leydig's cells nuclei were compared with those of the liver, kidney, hepatic and renal nuclei, in both whole tissue and the cellular nuclei the metal content was lower in the testis than in the liver and kidney. Leydig's cells were the most sensitive to Cd cytotoxicity although Cd uptake in this cell population was lesser than those in any other ones. Cd did not show any DNA damage in both testicular cell species. These results suggest that Cd induces testicular cancer by causing overall functional impairment of the organ or cytotoxicity to Leydig's cells, target cell population for Cd carcinogenecity.