DNA damaging activity of cadmium in Leydig cells, a target cell population for cadmium carcinogenesis in the rat testis.
To clarify the mechanism by which Cd initiates rat testicular cancer, the ability of Cd or H2O2 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. H2O2 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 H2O2 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 H2O2, which is generated by the metal exposure, rather than by a direct genotoxicity of Cd. The oxidant-mediated initiation is clearly a complicated event accomplished by multiple factors.
Koizumi
T
T
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Li
Z G
ZG
Tatsumoto
H
H
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000494:pharmacology; D015197:Carcinogenicity Tests; D004249:DNA Damage; D005296:Ferrous Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D016877:Oxidants / Q000633:toxicity; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000166:cytology / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology
D005296:Ferrous Compounds; D016877:Oxidants; D002104:Cadmium; D006861:Hydrogen Peroxide; D015032:Zinc; D002118:Calcium