Conversion of IQ to 7-OHIQ by gut microflora.

Abstract

The rates of conversion of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) to its reportedly mutagenic 7-keto derivative (7-OHIQ) by intestinal bacteria from humans, mice, and rats were compared. IQ was metabolized faster by cecal contents from rats or mice than by human fecal samples (113 and 87 mumol 7-OHIQ formed/hr/g cecal contents, respectively, vs. 12.3 mumol/hr/g feces). Cecal contents from germ-free rats colonized with human fecal bacteria [human flora-associated (HFA) rats] converted IQ to 7-OHIQ at rates generally lower than contents from rats colonized with their native flora. Diet had a marked effect on IQ metabolism by HFA rat cecal contents. The rate of IQ conversion to 7-OHIQ was increased in rats fed a diet high in beef dripping compared with that in rats fed a low-fat control diet. A diet high in olive oil, however, did not produce an increase in the IQ conversion rate. Addition of fiber to a purified diet increased the rate of IQ metabolism in the following order: sugar beet fiber > wheat bran > oat bran fiber > fiber-free diet. In a further study, HFA rats were fed human diets altered independently in their fat, fiber (wheat bran), and beef contents. The high-fiber diet produced the greatest increase in IQ conversion rate, followed by the high-fat diet. The diet with a high beef content and the control diet (low levels of all 3 macrocomponents) produced similarly low rates of IQ conversion. Material from incubations of IQ with HFA rat cecal contents, assumed to be 7-OHIQ on the basis of chromatographic behavior, was confirmed to be directly mutagenic, producing approximately 800 His+ revertants per microgram with S. typhimurium TA98.