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8-Hydroxylation of Guanine Bases in Kidney and Liver DNA of Hamsters Treated with Estradiol: Role of Free Radicals in Estrogen-induced Carcinogenesis¹

Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas 77555-1031

The chronic administration of estradiol induces a high incidence (80–100%) of renal tumors in male Syrian hamsters. As part of our examination 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 radical interaction with DNA, in livers and kidneys of hamsters treated with 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-OHdGua/10⁵dGua, respectively] and raised hepatic 8-OHdGua levels almost 4-fold over control values, respectively. These changes were observed in kidney 4 h and in liver 1 or 2 h after treatment of hamsters with estradiol. Estradiol implants administered to hamsters for 3 days raised renal levels of 8-OHdGua by 50% over control values. Six days after 17ß-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 radicals generated via redox cycling of catecholestrogen metabolites.

¹ Supported by the National Cancer Institute, NIH (CA 43233).

² To whom requests for reprints should be addressed.

Received 7/25/94. Accepted 9/20/94.

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