GENOTOXICITY AND CARCINOGENICITY IN RATS AND MICE OF DIHYDRO-3-METHYL-7H-IMIDAZOLO[4,5-F]QUINOLIN-7-ONE - AN INTESTINAL BACTERIAL METABOLITE OF 2-AMINO-3-METHYL-3H-IMIDAZO[4,5-F]QUINOLINE

Background: Compounds formed on the surface of fried or grilled meat a nd fish may be associated with increased risk of colon cancer. Normal intestinal bacteria can convert one of these compounds, 2-amino-3-meth yl-3H-imidazo[4,5-f]quinoline (IQ), to the 7-hydroxy metabolite, dihyd ro-3-methyl-7H-imidazolo[4,5-f]quinolin-7-one (7-OHIQ), a direct-actin g mutagen. Purpose: We studied the genotoxicity and carcinogenicity of 7-OHIQ to determine if it is responsible for the colon-specific activ ity of IQ. Methods: The effects of pure, synthetic 7-OHIQ on DNA were evaluated in the Ames Salmonella typhimurium TA98 test, with and witho ut an induced rat liver S9 fraction, and in the Williams DNA repair te st using freshly explanted rat hepatocytes. 7-OHIQ was also subjected to an in vivo bioassay for 21 months by long-term intrarectal infusion in male F344 rats, using IQ and N-nitrosomethylurea (NMU) given intra rectally as positive tumor-producing controls. The standard NIH-07 rod ent diet was supplemented with 15% corn oil to maximize any effect of the infused materials on the colon. A parallel bioassay involved intra peritoneal injection of 7-OHIQ in newborn mice, followed by dietary ad ministration from week 11 to week 67. Again, IQ and NMU were used as p ositive 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 newb orn mouse test it produced only a low incidence of liver neoplasms. Co nclusions: 7-OHIQ is not genotoxic, for to be so classified it must be definitely positive in both the Ames and Williams tests; moreover, it is not carcinogenic, in marked contrast to IQ and NMU.