Comparison of the protective effect of melatonin with other antioxidants in the hamster kidney model of estradiol-induced DNA damage

Abstract

17β-Estradiol (E 2) is a known carcinogen. Estrogen induction of tumors in hamster kidney is a model of estrogen-related carcinogenesis. Melatonin is a well-known antioxidant, free radical scavenger and oncostatic agent. Changes in the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), an index of DNA damage, were measured in kidneys, liver and testes from hamsters treated with E 2 (75 mg/kg b.w.) and collected 5 h later. Potential protective effects of melatonin, N-acetylserotonin (NAS), indole-3-propionic acid (IPA) and ascorbic acid (AA) against E 2-induced DNA damage were tested. The antioxidants were applied in equimolar doses of 64.5 μmol/kg b.w., 2 and 0.5 h before and 2 and 4 h after E 2 treatment. E 2 treatment caused a significant increase in 8-oxodGuo levels in kidneys, but did not influence significantly the oxidation of guanine bases in liver and testes. Melatonin, IPA and AA, but not NAS, completely prevented E 2-induced DNA damage in hamster kidneys. It is concluded that melatonin, IPA and AA may be effective in protecting against E 2-related DNA damage and, consequently, carcinogenesis.