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Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide
Author(s) -
Inoue Sumiko,
Kawanishi Shosuke
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00873-8
Subject(s) - peroxynitrite , chemistry , superoxide , nitric oxide , dna , oxidative phosphorylation , guanine , hydroxyl radical , dna damage , dna oxidation , incubation , biochemistry , nucleotide , radical , enzyme , organic chemistry , gene
Incubation of calf thymus DNA with 3‐morpholinosydnonimine (SIN‐1), which simultaneously generates nitric oxide (NO) and superoxide (O 2 − ), 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 32 P‐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 O 2 − to form peroxynitrite and the peroxynitrite induces oxidative DNA damage through an active intermediate of which reactivity is similar to •OH.

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