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 μmol 7‐OHIQ formed/hr/g cecal contents, respectively, vs. 12.3 μmol/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.