Existence of no-observed effect levels for 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline on hepatic preneoplastic lesion development in BN rats

• Published in: Cancer letters Vol. 231; no. 2; pp. 304 - 308
• Main Authors: Wei, Min, Hori, Taka-aki, Ichihara, Toshio, Wanibuchi, Hideki, Morimura, Keiichirou, Kang, Jin Seok, Puatanachokchai, Rawiwan, Fukushima, Shoji
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 18.01.2006; Elsevier Limited
• Subjects: 2-Amino-3,8-dimethylimidazo[4,5- f]quinoxaline; Animals; Cancer risk assessment; Carcinogens; Carcinogens - toxicity; Glutathione S-Transferase pi - metabolism; Hepatocarcinogenesis; Liver - drug effects; Liver - enzymology; Liver - pathology; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - enzymology; Male; Medical research; Mutation; No-observed effect level; No-Observed-Adverse-Effect Level; Precancerous Conditions - chemically induced; Precancerous Conditions - enzymology; Quinoxalines - toxicity; Rats; Rats, Inbred BN; Rats, Inbred F344; Rodents; Strain differences; Studies; Technological change; Japan; 2-Amino-3,8-dimethylimidazo[4,5- f]quinoxaline; Strain differences; GST-P; No-observed effect level; DEN; NOEL; 2-AFF; Hepatocarcinogenesis; MeIQx; 2-amino-3,8-dimethylimidazo[4,5- f] quinoxaline; Cancer risk assessment; 2-acetylaminofluorene; glutathione S-transferase placental form; diethylnirtrosamine
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2005.02.029

There is increasing evidence that dose–response curve of genotoxic carcinogen is nonlinear and a practical threshold dose exists. However, little is known about differences in the dose–response relationship of genotoxic carcinogen among different strain rats. Herein, we showed that low doses of genotoxic carcinogen 2-amino-3,8-dimethylimidazo[4,5- f] quinoxaline (MeIQx) had no effects on induction of liver glutathione S-transferase placental form (GST-P)-positive foci in both BN and F344 rats, and therefore demonstrated the existence of no-observed effect level for hepatocarcinogenicity of this genotoxic carcinogen irrespective of strains. These findings further support our notion that a practical threshold dose for MeIQx hepatocarcinogenicity exists in rats.