DNA damaging activity of cadmium in Leydig cells, a target cell population for cadmium carcinogenesis in the rat testis

Abstract

To clarify the mechanism by which Cd initiates rat testicular cancer, the ability of Cd or H 2O 2 to induce DNA single strand breakage was evaluated in testicular Leydig cells using a simple and rapid DNA precipitation method. Effects of Cd, Fe, Zn and Ca on the oxidant-induced DNA damage and effects of reduced glutathione (GSH) on the genotoxicity caused by the peroxide and/or Fe were also assessed. H 2O 2 induced strong DNA single strand breakage. Cd alone did not exhibit such a genotoxicity nor did it enhance the peroxide-induced DNA damage. Ca and Fe(II) potentiated the oxidant-induced DNA single strand breakage, while Zn partially protected cells from the oxidative damage of DNA caused by the peroxide. GSH attenuated single strand breaks of DNA brought about by H 2O 2 and/or Fe. These results suggest that the initiation of carcinogenesis in the rat testis by Cd is triggered by active oxygen species such as H 2O 2, which is generated by the metal exposure, rather than by a direct genotoxicity of Cd. The oxidantmediated initiation is clearly a complicated event accomplished by multiple factors.