Comparison of the protective effect of melatonin with other antioxidants in the hamster kidney model of estradiol-induced DNA damage.
17beta-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) (75mg/kg b.w.) and collected 5h 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 micromol/kg b.w., 2 and 0.5h before and 2 and 4h 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.
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
M
M
Karbownik
R J
RJ
Reiter
J
J
Cabrera
J J
JJ
Garcia
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D006224:Cricetinae; D004249:DNA Damage; D004958:Estradiol / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D008550:Melatonin / Q000494:pharmacology*; D008647:Mesocricetus
D000975:Antioxidants; D004958:Estradiol; D008550:Melatonin