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

Japanese Journal of Cancer Research : Gann
T KatoT Shirai

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 six weeks, and partially hepatectomized 1 week after the beginning of MeIQx administration. Quantitative values for glutathione S-transferase placental form (GST-P)-positive 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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Citations

Apr 11, 2001·Mutation Research·K El-Bayoumy
Jan 8, 1999·Mutation Research·Y Kuroda, Y Hara
Jul 11, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Tridib ChakrabortyMalay Chatterjee
Mar 31, 1999·Free Radical Research·S LoftH E Poulsen
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Jun 8, 1999·Japanese Journal of Cancer Research : Gann·M MurataS Kawanishi
Jul 9, 1999·Environmental and Molecular Mutagenesis·W J MeehanG K Ostrander
Mar 16, 2002·Carcinogenesis·Emmanuelle TavanPierrette Cassand
Apr 12, 2002·International Journal of Cancer. Journal International Du Cancer·Tokuo SukataShoji Fukushima
Nov 10, 2013·Cancers·Anna KakehashiHideki Wanibuchi
Jun 17, 2020·Archives of Toxicology·Andrea HartwigGerhard Eisenbrand

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