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.