Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide.
Incubation of calf thymus DNA with 3-morpholinosydnonimine (SIN-1), which simultaneously generates nitric oxide (NO) and superoxide (O2-), induced a significant increase of 8-hydroxydeoxyguanosine (8-OH-dG). Peroxynitrite also increased 8-OH-dG in calf thymus DNA. Addition of free hydroxyl radical (.OH) scavengers inhibited the increase of 8-OH-dG by SIN-1 or peroxynitrite. Incubation of 32P-labeled DNA fragment with SIN-1 or peroxynitrite caused DNA cleavage at every nucleotide with a little dominance at guanine residues. The results suggest that NO reacts with O2- to form peroxynitrite and the peroxynitrite induces oxidative DNA damage through an active intermediate of which reactivity is similar to .OH.
Inoue
S
S
Department of Public Health, Graduate School of Medicine, Kyoto University, Japan.
Kawanishi
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D003854:Deoxyribonucleotides / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism*
D003854:Deoxyribonucleotides; D016166:Free Radical Scavengers; D009566:Nitrates; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; C002385:linsidomine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D008981:Molsidomine; D003849:Deoxyguanosine