Effects of carbon dioxide/bicarbonate on induction of DNA single-strand breaks and formation of 8-nitroguanine, 8-oxoguanine and base-propenal mediated by peroxynitrite.
Carbon dioxide has been reported to react with peroxynitrite (ONOO-), a strong oxidant and nitrating agent, to form an ONO2CO2- adduct, altering the reactivity characteristic of peroxynitrite. We found that bicarbonate (0-10 mM) caused a dose-dependent increase of up to 6-fold in the formation of 8-nitroguanine in calf-thymus DNA incubated with 0.1 mM peroxynitrite, whereas it produced no apparent effect on 8-oxoguanine formation. In contrast, bicarbonate inhibited peroxynitrite-induced strand breakage in plasmid pBR322 DNA and thymine-propenal formation from thymidine. We conclude that C02/HCO3- reacts with peroxynitrite to form a potent nitrating agent, but also to inactivate hydroxyl-radical-like activity of peroxynitrous acid.
Yermilov
V
V
Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, Lyon, France.
Yoshie
Y
Y
Rubio
J
J
Ohshima
H
H
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000494:pharmacology*; D002417:Cattle; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D006147:Guanine / Q000031:analogs & derivatives / Q000096:biosynthesis*; D009566:Nitrates / Q000378:metabolism*; D013941:Thymine / Q000031:analogs & derivatives* / Q000096:biosynthesis
C095838:8-nitroguanine; D001639:Bicarbonates; D004277:DNA, Single-Stranded; D009566:Nitrates; D002245:Carbon Dioxide; C039642:peroxynitric acid; C024829:8-hydroxyguanine; D006147:Guanine; C044551:3-(thymin-1'-yl)-2-propenal; D013941:Thymine