Effective inhibition by beta-carotene of cellular DNA breaking induced by peroxynitrous acid.
Peroxynitrous acid synthesized by reaction of hydrogen peroxide and nitrite and generated from 3-morpholinosydononimine (SIN-1) induced cellular DNA breaking of human promyelocytic leukemia HL-60 cells in phosphate buffer (pH 7.5) as assessed by alkaline single cell gel electrophoresis (comet) assay and quantification of comet types. Ascorbate and Trolox inhibited cellular DNA breaking induced by peroxynitrous acid, but the concentrations of these antioxidants required for effective inhibition was about 50-fold higher than that of peroxynitrous acid. beta-Carotene protected DNA breaking by peroxynitrous acid in 20% tetrahydrofuran-phosphate buffer (pH 7.5) much more effectively than ascorbate and Trolox. The concentrations of beta-carotene required for effective inhibition was lower than the concentration of peroxynitrous acid.
Hiramoto
K
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Tomiyama
S
S
Kikugawa
K
K
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D016166:Free Radical Scavengers / Q000494:pharmacology; D005663:Furans; D018922:HL-60 Cells; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008981:Molsidomine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009608:Nitrous Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D030421:Peroxynitrous Acid; D012995:Solubility; D013011:Sorbic Acid / Q000494:pharmacology; D013997:Time Factors; D019207:beta Carotene / Q000494:pharmacology*
D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D005663:Furans; D019207:beta Carotene; D030421:Peroxynitrous Acid; C018674:tetrahydrofuran; D008353:Mannitol; C002385:linsidomine; D004247:DNA; D008981:Molsidomine; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D009608:Nitrous Acid; D013011:Sorbic Acid; D004121:Dimethyl Sulfoxide