2-Hydroxyadenine, a mutagenic form of oxidative DNA damage, is not repaired by a glycosylase type mechanism in rat organs.
Oxygen radicals are known to play a role in causing cellular DNA damage, which is involved in carcinogenesis. 8-Hydroxyguanine (8-OH-Gua) is a major form of oxidative DNA damage and is known as a useful marker of DNA oxidation. Recently, we found another type of oxidative DNA damage, 2-hydroxyadenine (2-OH-Ade), which has a mutation frequency comparable to that of 8-OH-Gua. We compared the repair activities for two types of oxidative DNA damage, 8-OH-Gua and 2-OH-Ade, in 7-week-old male Sprague-Dawley (SD) rat organs. The repair activities were measured by an endonuclease nicking assay using 22 mer [32P]-end-labeled double-stranded DNA substrates, which contained either 8-OH-Gua (opposite C) or 2-OH-Ade (opposite T or C). In all of the SD rat organs we studied, the nicking activity for 2-OH-Ade was not detected, while that for 8-OH-Gua was clearly detected with the same conditions. Moreover, the 2-OH-Ade nicking activity was not induced in Wistar rat kidney extracts prepared after ferric nitrilotriacetate (Fe-NTA) treatment, which is known to increase 8-OH-Gua repair activity. These results suggest that 2-OH-Ade might not be repaired by the glycosylase type mechanism in mammalian cells.
Tsurudome
Y
Y
Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Hirano
T
T
Kamiya
H
H
Yamaguchi
R
R
Asami
S
S
Itoh
H
H
Kasai
H
H
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004720:Endonucleases / Q000378:metabolism*; D005290:Ferric Compounds / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D005290:Ferric Compounds; C024829:8-hydroxyguanine; D006147:Guanine; C008183:isoguanine; D004720:Endonucleases; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate