8-HYDROXYLATION OF GUANINE BASES IN KIDNEY AND LIVER DNA OF HAMSTERS TREATED WITH ESTRADIOL - ROLE OF FREE-RADICALS IN ESTROGEN-INDUCED CARCINOGENESIS

The chronic administration of estradiol induces a high incidence (80-1 00%) of renal tumors in male Syrian hamsters. As part of our examinati on of a mechanism of carcinogenesis by free radicals generated during redox cycling of catecholestrogen metabolites, we assayed levels of 8- hydroxy-2'-deoxyguanosine (8-OHdGua), a marker product of hydroxy radi cal interaction with DNA, in livers and kidneys of hamsters treated wi th estradiol. Injections of 50 and 100 mg/kg estradiol doubled renal 8 -OHdGua levels over controls [10.0 +/- 0.1 (SD) and 5.4 +/- 0.4 8-OHdG ua/10(5)dGua, respectively and raised hepatic 8-OHdGua levels almost 4 -fold over control values, respectively. These changes were observed i n kidney 4 h and in liver 1 or 2 h after treatment of hamsters with es tradiol. Estradiol implants administered to hamsters for 3 days raised renal levels of 8-OHdGua by 50% over control values. Six days after 1 7 beta-estradiol implantation, 8-OHdGua levels returned to near-normal values. Liver DNA was not affected by estradiol implants. These data support a mechanism of estrogen-induced carcinogenesis by free radical s generated via redox cycling of catecholestrogen metabolites.