title: Role of iron in estrogen-induced cancer.
abstract: Redox cycling of catecholestrogen metabolites between quinone and catechol forms is a mechanism of generating potentially mutagenic oxygen radicals in estrogen-induced carcinogenesis. Consistent with this concept, multiple forms of oxygen radical-generated DNA damage are induced by estrogen in cell-free systems, in cells in culture and in rodents prone to estrogen-induced cancer. Metal ions, specifically iron, are necessary for the production of hydroxy radicals. Iron has not received much attention in discussions of estrogen-induced carcinogenesis and human hormone-associated cancer, and is the focus of this review. An elevated dietary iron intake enhances the incidence of carcinogen-induced mammary cancer in rats and estrogen-induced kidney tumors in Syrian hamsters. Estrogen administration increases iron accumulation in hamsters and facilitates iron uptake by cells in culture. In humans, elevated body iron storage has been shown to increase the risk of several cancers including breast cancer. A role of iron in hormone-associated cancer in humans offers attractive routes for cancer prevention by regulating metal ion metabolism and interfering with iron accumulation in tissues.
authors.affiliation: Stehlin Foundation for Cancer Research, 1918 Chenevert, Houston, TX 77003, USA. jliehr@stehlin.org
authors.forename: J G
authors.initials: JG
authors.lastname: Liehr
authors.forename: J S
authors.initials: JS
authors.lastname: Jones
mesh_terms: D000818:Animals; D001711:Biotransformation; D003043:Cocarcinogenesis; D004347:Drug Interactions; D004967:Estrogens / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000633:toxicity*; D009153:Mutagens / Q000378:metabolism; D009369:Neoplasms / Q000139:chemically induced*; D010084:Oxidation-Reduction
chemical_list: D004967:Estrogens; D009153:Mutagens; D017665:Hydroxyl Radical; D007501:Iron