Site-specific DNA damage induced by sulfite in the presence of cobalt(II) ion. Role of sulfate radical.
The reactivities of sulfite (SO23-) with DNA in the presence of metal ions were investigated by a DNA sequencing technique using 32P-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene. Sulfite caused DNA damage in the presence of Co2+, Cu2+ and Mn2+, although sulfite alone or metal ion alone did not. The order of inducing effect on sulfite-dependent DNA damage (Co2+ much greater than Cu2+ greater than Mn2+ Fe3+) was consistent with that of accelerating effect on the initial oxygen consumption rate of sulfite autoxidation. The DNA damage induced by sulfite plus Co2+ was inhibited by 3,5-dibromo-4-nitrobenzenesulfonate, primary and secondary alchols, whereas it was not inhibited by SOD, catalase and tert-butyl alcohol. Incubation of DNA with sulfite plus Co2+ followed by the piperidine treatment led to the predominant cleavage at the positions of guanine especially located 5' to guanine. Sulfite plus Cu2+ gave a DNA cleavage pattern different from that induced by sulfite plus Co2+. The photolysis of peroxydisulfate (S2O28-), which is known to produce SO-4 radicals, gave a DNA cleavage pattern similar to that induced by sulfite plus Co2+. ESR studies using spin-trapping reagent revealed the production of spin adduct possibly of SO-3 radical in a solution of sulfite plus Cu2+, whereas much less spin adduct was produced by sulfite plus Co2+. The results suggest that sulfite is rapidly autoxidized in the presence of Co2+ to produce SO4- radical causing site-specific DNA damage.
Kawanishi
S
S
Department of Public Health, Faculty of Medicine, Kyoto University, Japan.
Yamamoto
K
K
Inoue
S
S
D000438:Alcohols / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D005609:Free Radicals; D010084:Oxidation-Reduction; D013431:Sulfates / Q000378:metabolism*; D013447:Sulfites / Q000378:metabolism / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D000438:Alcohols; D005609:Free Radicals; D013431:Sulfates; D013447:Sulfites; D003035:Cobalt; D003300:Copper; D004247:DNA; D013482:Superoxide Dismutase