Analyses of oxidative DNA damage and its repair activity in the livers of 3'-methyl-4-dimethylaminoazobenzene-treated rodents.
We measured the levels of 8-hydroxyguanine (8-OH-Gua) and its repair activity in the livers of the Donryu rat, the carcinogen-resistant DRH rat, and the ddy mouse, which were fed a 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)-containing diet. In a short-term rat experiment (maximum 2 months), 3'-MeDAB did not increase the 8-OH-Gua levels in the livers of the two rat strains, although it significantly increased the repair activity in only the Donryu rat liver at 1 and 2 months. After long-term 3'-MeDAB administration to the ddy mouse (8 months), the levels of 8-OH-Gua and its repair activity were increased in the liver by 3.6-fold and 1.6-fold, respectively. These experiments suggest that 3'-MeDAB increases 8-OH-Gua generation in rodent liver DNA and the 8-OH-Gua repair assay is a reliable marker of cellular oxidative stress induced by carcinogens.
Department of 1 Environmental Oncology, University of Occupational and Environmental Health, Japan. h-kasai@med.uoeh-u.ac.jp
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Hirano
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Higashi
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Sakai
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Tsurudome
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Ootsuyama
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Kido
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Kasai
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004396:Coloring Agents / Q000633:toxicity*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D043382:DNA-Formamidopyrimidine Glycosylase; D004198:Disease Susceptibility; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity*; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D002273:Carcinogens; D004396:Coloring Agents; D012333:RNA, Messenger; D008749:Methyldimethylaminoazobenzene; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase