Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
100
Journal Issue
9
Pages
5390-5395
Date Issued
2003
Author(s)
Abstract
Modulation of the cytotoxicity and mutagenicity of 4-hydroxyestradiol (4-OHE2), an oxidative metabolite of estrogen, by antioxidants was assessed in human MCF7 cells and TK-6 lymphoblast cells. The cytotoxicity of the catecholic estrogens was potentiated by depletion of intracellular glutathione and was independent of oxygen concentration. Agents such as the nitroxide Tempol can facilitate the oxidation of the semiquinone to the Q and enhanced 4-OHE2 cytotoxicity. Conversely, reducing agents such as ascorbate, cysteine, and 1,4-dihydroxytetramethylpiperidine (THP) protected against cytotoxicity and decreased mutation induction, presumably by reducing the semiquinone to the hydroquinone. Our results support the proposition that oxidation of the semiquinone to the corresponding Q is crucial in eliciting the deleterious effects of catecholic estrogens. Furthermore, because the deleterious effects of 4-OHE2 were abrogated by dietary and synthetic antioxidants, our results would support the chemopreventive use of diets rich in reducing substances (vitamins and added synthetic antioxidants) as a means of decreasing the risks associated with estrogen exposure and developing of breast cancer.
Other Subjects
1,4 dihydroxytetramethylpiperidine; 4 hydroxyestradiol; antioxidant; ascorbic acid; catechol; cysteine; estrogen; glutathione; oxygen; piperidine derivative; semiquinone; tempol; unclassified drug; article; breast cancer; cell culture; cell survival; chemoprophylaxis; controlled study; cytotoxicity; electron spin resonance; human; human cell; mutagenesis; oxygen concentration; priority journal; Antioxidants; Cell Line; Electron Spin Resonance Spectroscopy; Estrogens, Catechol; Free Radicals; Humans; Mutagenesis; Quinones
Type
journal article