Genotoxicity and Carcinogenicity in Rats and Mice of 2-Amino-3, 6- dihydro-3-methyl-7H-imidazolo [4, 5-f]quinolin-7-one: an Intestinal Bacterial an Intestinal Bacterial Metabolite of 2-Amino-3-methyl-3H-imidazo[4, 5-f]quinoline

• Published in: JNCI : Journal of the National Cancer Institute 1994-01, Vol.86 (1), p.25-30
• Main Authors: Weisburger, John H., Rivenson, Abraham, Reinhardt, Joel, Aliaga, Cesar, Braley, Joanne, Dolan, Lisa M., Williams, Gary M., Zang, Edith, Kingston, David G. I., Bashir, Mohammed, Shu, Yue-Zhong, Wilkins, Tracy D., Tassell, Roger L. Van
• Format: Article
• Language: English
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/86.1.25

Background Compounds formed on the surface of fried or grilled meat and fish may e associated with increased risk of colon cancer. Normal intestinal bacteria can convert one of these compounds, 2-amino-3-methyl-3H-imidazo[4, 5-f]quinoline (IQ), to the 7-hydroxy metabolite, 2-amino-3, 6-dihydro-3-methyl-7H- imidazolo[4, 5-f]quinolin-7-one (7-OHIQ), a direct-acting mutagen. Purpose: We studied the genotoxicity and determine if it is responsible for the colon-specific activity of IQ. Methods The effects of pure, synthetic 7-OHIQ on DNA were evaluted in the Ames Salmonella typhimurium TA98 test, with and without an induced rat liver S9 fraction, and in the Williams DNA repair test using freshly explanted rat hepatocytes. 7-OHIQ was also subjected to an in vivo bioassay for 21 months by long-term intrarectal infulsion in male F344 rats, using IQ and N-nitrosomethylurea (NMU) given intrarectally controls. The standard NIH-07 rodent diet was supplemented with 15% corn oil to maximize any effect of the infused materials on the colon. A parallel bioassay involved intraperitoneal injection of 7-OHIQ in newborn mice, followed by dietary administration from week 11 to week 67. Again, IQ and NMU were used as positive controls. Results We confirmed that 7-OHIQ is a direct-acting mutagen in the Ames test, with added S9 liver fraction giving higher mutagenicity. 7-OHIQ was negative in the Williams test, whereas IQ was positive. 7-OHIQ did not induce colon cancer in rats, and in the newborn mouse test it produced only a low incidence of liver neoplasms. Conclusions 7-OHIQ is not genotoxic, for to be so classified it must be definitely positive in both the Ames and Williams test; moreover, it is not carcinogenic, in marked contrast to IQ and NMU. [J Natl Cancer Inst 86:25–30, 1994]