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Iron participates in the generation of hydroxyl radicals by the iron-catalyzed Fenton reaction. Its role in estrogen-induced carcinogenesis has been examined in this study by investigating the effects of iron content of hamster diets on tumor induction by estradiol. The renal tumor incidence and number of tumor nodules in hamsters treated with estradiol plus a diet enriched with iron (384 p.p.m. Fe as ferric citrate) for 5 months were 2- and 4-fold higher, respectively, than those observed in animals on an iron-poor diet plus estradiol (3.9 p.p.m. Fe, as ferric citrate). Tumor incidence and number of tumor nodules in estradiol-treated hamsters on the iron-deficient diet were not different from those of animals on a normal rodent chow. No tumors were detected in hamsters treated only with the low or high iron diets. Total serum iron was significantly increased in animals treated with the high iron diet plus estradiol compared with the low iron diet plus estradiol group and the high and low iron controls. Estrogen treatment increased non-heme iron in liver of both high and low iron treatment groups and in kidney of the hamsters on the low iron diet. It is concluded that dietary iron enrichment enhances the incidence and severity of estrogen-induced tumor induction.

Enhancement of estrogen-induced renal tumorigenesis in hamsters by dietary iron