title: An o-quinone form of estrogen produces free radicals in human breast cancer cells: correlation with DNA damage.
abstract: The o-quinone forms of 2,3- and 3,4-catechol estrogens have been implicated in the carcinogenicity of these hormones. The concomitant production of reactive oxygen species during reduction of the o-quinone estrogens has been inferred to play a mechanistic role in their mutagenic potential. Conclusive evidence documenting the production of hydrogen peroxide, the hydroxyl radical, and the estrone 3,4-semiquinone in estrone 3,4-quinone (3,4-EQ)-treated human breast cancer subcellular fractions was demonstrated in the absence of exogenously added catalysts. Subcellular fractions of MCF-7 cells treated with 3,4-EQ and NADPH, including nuclei, mitochondria, and microsomes, were shown to support significant amounts of hydrogen peroxide production. Hydrogen peroxide production in 3,4-EQ-treated cellular fractions and the chromosomal DNA damage induced in 3,4-EQ-treated MCF-7 cells were abolished by the addition of catalase. A significant and potentially physiologically relevant spontaneous reduction of 3,4-EQ by NADPH resulting in hydrogen peroxide production was demonstrated. The results unequivocally demonstrate that free radicals are produced during the metabolism of estrone 3,4-quinone in human cells.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis 55455.
authors.forename: L M
authors.initials: LM
authors.lastname: Nutter
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wu
authors.forename: E O
authors.initials: EO
authors.lastname: Ngo
authors.forename: E E
authors.initials: EE
authors.lastname: Sierra
authors.forename: P L
authors.initials: PL
authors.lastname: Gutierrez
authors.forename: Y J
authors.initials: YJ
authors.lastname: Abul-Hajj
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D004963:Estrenes / Q000378:metabolism / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism / Q000633:toxicity*; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D011809:Quinones / Q000378:metabolism; D017382:Reactive Oxygen Species; D013347:Subcellular Fractions / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D004963:Estrenes; D004967:Estrogens; D005609:Free Radicals; D011809:Quinones; D017382:Reactive Oxygen Species; C044208:1,5(10)-estradiene-3,4,17-trione; D006861:Hydrogen Peroxide