title: Prevention of quinone-mediated DNA arylation by antioxidants.
abstract: High performance liquid chromatographic (HPLC) analysis showed that the prototype antioxidant ascorbate (vitamin C) inhibits the DNA adducts induced by synthetic estrogen diethylstilbestrol (DES) and the antiestrogen metabolite 4-hydroxytamoxifen (4-OHTam). Treatment of salmon testes DNA with 4-OHTam quinone or 4-OHTam in the presence of horseradish peroxidase and hydrogen peroxide (H(2)O(2)) generated the same DNA adduct profile. Vitamin C and N-acetylcysteine (NAC) inhibited the formation of 4-OHTam-dG adducts in a dose-dependent manner. To determine whether the same antioxidants also protect cellular DNA, HL-60 cells were used as cell culture model. Cells treated with 10 microM 4-OHTam in the presence of 1 microM H(2)O(2 )for 24 h gave 4-OHTam-dG adducts approximately 4 x 10(-7), n = 3. Treatment of the cells with 100 microM 4-OHTam, without H(2)O(2), produced the same level of adducts. Supplementation of the incubation media with vitamin C (2.5 mM) or NAC (5 mM) inhibited the formation of DNA adducts. Thus, antioxidants may protect susceptible cells from genotoxicity associated with 4-OHTam activation.
authors.affiliation: Department of Molecular and Cellular Biophysics, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: H K
authors.initials: HK
authors.lastname: Slocum
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018736:DNA Adducts / Q000187:drug effects* / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000378:metabolism* / Q000494:pharmacology*; D006735:Horseradish Peroxidase; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D012474:Salmon; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013737:Testis
chemical_list: D000975:Antioxidants; D018736:DNA Adducts; C068149:diethylstilbesterol-DNA adduct; D013629:Tamoxifen; C016601:afimoxifene; D004054:Diethylstilbestrol; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D001205:Ascorbic Acid; D000111:Acetylcysteine