Increase in the 8-hydroxyguanine repair activity in the rat kidney after the administration of a renal carcinogen, ferric nitrilotriacetate.
One type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), is known to increase in rat kidney DNA after the administration of a renal carcinogen, ferric nitrilotriacetate (Fe-NTA). To determine the involvement of oxygen radicals in Fe-NTA carcinogenesis, we examined whether the 8-OH-Gua repair enzymes are induced in the rat kidney after Fe-NTA administration, in addition to our analysis of the 8-OH-Gua levels in the DNA, because the 8-OH-Gua repair activity is known to be induced in mammalian cells by oxidative stress due to ionizing radiation. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22-mer double strand DNA, which contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua repair activity was observed in the rat kidney after a single intraperitoneal injection of Fe-NTA (p < 0.01). This is the first report on the induction of the repair activity for 8-OH-Gua after treatment with a chemical carcinogen. This assay will be useful for evaluating the carcinogenicity of oxygen radical-forming chemicals.
Yamaguchi
R
R
Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Hirano
T
T
Asami
S
S
Sugita
A
A
Kasai
H
H
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004720:Endonucleases / Q000096:biosynthesis / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D005290:Ferric Compounds; C024829:8-hydroxyguanine; D006147:Guanine; D004720:Endonucleases; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate