8-Oxoguanine induces intramolecular DNA damage but free 8-oxoguanine protects intermolecular DNA from oxidative stress.
7,8-Dihydro-8-oxoguanine (8-oxoguanine; 8-oxo-G), one of the major oxidative DNA adducts, is highly susceptible to further oxidation by radicals. We confirmed the higher reactivity of 8-oxo-G toward reactive oxygen (singlet oxygen and hydroxyl radical) or nitrogen (peroxynitrite) species as compared to unmodified base. In this study, we raised the question about the effect of this high reactivity toward radicals on intramolecular and intermolecular DNA damage. We found that the amount of intact nucleoside in oligodeoxynucleotide containing 8-oxo-G decreased more by various radicals at higher levels of 8-oxo-G incorporation, and that the oligodeoxynucleotide damage and plasmid cleavage by hydroxyl radical were inhibited in the presence of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG). We conclude that 8-oxo-G within DNA induces intramolecular DNA base damage, but that free 8-oxo-G protects intermolecular DNA from oxidative stress. These results suggest that 8-oxo-G within DNA must be rapidly released to protect DNA from overall oxidative damage.
Kim
Ja-Eun
JE
Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-799, Seoul, South Korea.
Choi
Seongwon
S
Yoo
Ju-Ah
JA
Chung
Myung-Hee
MH
D001482:Base Composition; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress; D010957:Plasmids / Q000737:chemistry / Q000235:genetics
D016166:Free Radical Scavengers; D005609:Free Radicals; D009841:Oligonucleotides; D016877:Oxidants; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA