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 (80-100%) 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/10(5) dGua, 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 17 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 radicals generated via redox cycling of catecholestrogen metabolites.
Han
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Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031.
Liehr
J G
JG
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D006224:Cricetinae; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004054:Diethylstilbestrol; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D002393:Estrogens, Catechol; D005609:Free Radicals; D006900:Hydroxylation; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus
D004343:Drug Implants; D002393:Estrogens, Catechol; D005609:Free Radicals; D004958:Estradiol; D004054:Diethylstilbestrol; D000080242:8-Hydroxy-2'-Deoxyguanosine; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol; D003849:Deoxyguanosine