Dose-dependent Induction of 8-Hydroxyguanine and Preneoplastic Foci in Rat Liver by a Food-derived Carcinogen, 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline, at Low Dose Levels |
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Authors: | Toshio Kato Ryohei Hasegawa Dai Nakae Masao Hirose Makoto Yaono Lin Cui Yozo Kobayashi Yoichi Konishi Nobuyuki Ito Tomoyuki Shirai |
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Affiliation: | First Department of Pathology, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467;Department of Oncologic Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho, Kashihara 634;Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467 |
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Abstract: | Male F344 rats were administered 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline (MeIQx) in the diet at doses of 200, 50, 12.5, 3.2, 0.8, 0.2 and 0.05 ppm for 6 weeks, and partially hepatectomized 1 week after the beginning of MeIQx administration. Quantitative values for glutathione S-transferase placental form (GST-P)-positiye foci in the liver were dose-dependently increased by the MeIQx treatment. 8-Hydroxyguanine (8-OHG) levels assessed after 1 week of dietary MeIQx administration were also dose-dependently increased, although the effect was no longer observed at the end of the treatment period. The correlation between numbers of GST-P-positive foci at week 6 and 8-OHG levels at week 1 was linear, values for both parameters being higher than the control levels even in the 0.8 ppm dose group. These findings indicate that, in addition to the previously reported MeIQx-DNA adduct formation, DNA modifications due to oxidative damage may play an important role in MeIQx liver carcinogenesis in rats. |
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Keywords: | GST-P-positive foci 8-Hydroxyguanine MeIQx Liver carcinogenesis Rat |
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