Role of oxidative stress in single-dose, cadmium-induced testicular cancer.
Treatment of rats with a single carcinogenic dose of CdCl2 (i.e., 30 mumol/kg) caused severe hemorrhagic damage in the testis within the first 12 h after the metal. Subsequently, atrophy with calcification developed in the next 2-3 mo. Atrophied tissues regenerated during the 1 yr after exposure. Twelve hours after exposure to the Cd treatment, lipid peroxidation levels, Fe content, and cellular production of H2O2 were remarkably elevated in testicular Leydig cells, the target cell population for Cd carcinogenesis. At the same time, glutathione peroxidase activity rose, glutathione reductase and catalase activities were reduced, and superoxide dismutase activity was unchanged. Xanthine oxidase activity in Leydig cells was also elevated at 6 and 9 h after the Cd treatment. Reduced glutathione in testes was decreased and oxidized glutathione was increased 12 h after exposure to the metal. These facts suggest that the carcinogenic doses of Cd induced oxidative stress while compromising cellular defense mechanisms against such stress. Therefore, active oxygen species such as H2O2 may have an important role in the initiation of carcinogenesis within the target cell population.
Koizumi
T
T
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Li
Z G
ZG
D000818:Animals; D001284:Atrophy; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D019256:Cadmium Chloride; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D006470:Hemorrhage / Q000139:chemically induced; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007501:Iron / Q000032:analysis; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology; D015227:Lipid Peroxidation; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012038:Regeneration; D013736:Testicular Neoplasms / Q000139:chemically induced*; D013737:Testis / Q000737:chemistry / Q000187:drug effects*; D014969:Xanthine Oxidase / Q000378:metabolism; D015032:Zinc / Q000032:analysis
D002712:Chlorides; D002104:Cadmium; D006861:Hydrogen Peroxide; D007501:Iron; D014969:Xanthine Oxidase; D005978:Glutathione; D015032:Zinc; D019256:Cadmium Chloride; D002118:Calcium