Changes in activities of free radical detoxifying enzymes in kidneys of male Syrian hamsters treated with estradiol.
Target organ-specific estrogen-induced DNA adducts were previously shown to precede renal carcinogenesis in Syrian hamsters. Because estrogens induced these DNA modifications, but were not part of the adduct structure, free radical activation of endogenous electrophiles was postulated as a mechanism of tumor induction by estrogens. In the present study, the activities of enzymes which detoxify reactive intermediates were studied in liver and kidney of hamsters treated with estradiol for 1, 2, and 4 mo and in untreated controls. These studies were done to detect oxidative stress in the target organ of carcinogenesis. In the estrogen-exposed hamster kidney (1, 2, and 4 mo), activities of glutathione peroxidases I and II were significantly increased. The activity of catalase was decreased compared to those in untreated controls. In livers which are not the target organ of carcinogenesis, treatment of hamsters with estrogen for 1, 2, and 4 mo resulted in changes of activities of glutathione peroxidases I and II and catalase, which were opposite to the pattern found in the kidney. Activities of superoxide dismutase, glutathione reductase, glucose-6-phosphate dehydrogenase, gamma-glutamyl transpeptidase, and glutathione transferase in estradiol-treated hamster liver and kidney did not differ significantly from those in either liver or kidney of untreated age-matched controls. Fluorescent products of lipid peroxidation more than doubled in the kidney, but not in the liver of hamsters treated with estradiol for 1 mo. It is concluded that the increases in glutathione, in the activity of glutathione peroxidase, and in products of lipid peroxidation in the kidneys of hamsters treated chronically with estrogen all point towards elevated levels of oxidative stress.
Roy
D
D
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550-2774.
Liehr
J G
JG
D000818:Animals; D002374:Catalase / Q000032:analysis; D006224:Cricetinae; D004967:Estrogens / Q000633:toxicity*; D005453:Fluorescence; D005609:Free Radicals; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000032:analysis; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D013482:Superoxide Dismutase / Q000032:analysis
D004967:Estrogens; D005609:Free Radicals; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione