Abstract 5553: Low-dose carcinogenicity of 2-amino-3-methylimidazo[4,5- f ]quinoline in rats: Evidence for the existence of no-effect levels and a mechanism involving p21Cip/WAF1

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8_Supplement; p. 5553
• Main Authors: Wei, Min, Kakehashi, Anna, Yamano, Shotaro, Fukushima, Shoji, Wanibuchi, Hideki
• Format: Journal Article
• Language: English
• Published: 15.04.2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-5553

Abstract The carcinogenicity of the low amounts of genotoxic carcinogens present in food is of pressing concern. The purpose of the present study was to determine the carcinogenicity of low doses of the dietary genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and to investigate mechanisms by which IQ exerts its carcinogenic effects. A total of 1595 male F344 rats were divided into 7 groups and administered IQ at doses of 0, 0.001, 0.01, 0.1, 1, 10 and 100 ppm in the diet for 16 weeks. We found that IQ doses of 1 ppm and below did not induce preneoplastic lesions in either the liver or the colon, while IQ doses of 10 and 100 ppm induced preneoplastic lesions in both these organs. These results demonstrate the presence of no effect levels of IQ for both liver and colon carcinogenicity in rats and indicate that the dose-response relationship for IQ carcinogenicity is nonlinear. The finding that p21Cip/WAF1 was significantly induced in the liver at doses well below those required for IQ mediated carcinogenic effects, suggests that induction of p21Cip/WAF1 is one of the mechanisms responsible for the observed no-effect of low doses of IQ. Furthermore, IQ administration caused significant induction of CYP1A2 at doses of 0.01 to 10 ppm, but administration of 100 ppm IQ induced CYP1A1 rather than CYP1A2. This result indicates the importance of dosage when interpreting data on the carcinogenicity and metabolic activation of IQ. Overall, our results argue for the existence of a practical carcinogenic threshold for this genotoxic compound. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5553. doi:10.1158/1538-7445.AM2011-5553