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Applied and Environmental Microbiology, September 2005, p. 5116-5123, Vol. 71, No. 9
0099-2240/05/$08.00+0 doi:10.1128/AEM.71.9.5116-5123.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Bruno Combourieu,2,
Marja-Liisa Väisänen,1
Jean-Pierre Furet,1
Anne-Marie Delort,2 and
Sylvie Rabot1*
Institut National de la Recherche Agronomique, Unité d'Ecologie et de Physiologie du Système Digestif, Jouy-en-Josas, France,1 Centre National de la Recherche Scientifique, Université Blaise Pascal, Laboratoire de Synthèse et Etude de Systèmes d'Intérêt Biologique (UMR 6504), Aubière, France2
Received 3 December 2004/ Accepted 5 April 2005
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a mutagenic/carcinogenic compound formed from meat and fish during cooking. Following ingestion, IQ is metabolized mainly by liver xenobiotic-metabolizing enzymes, but intestinal bacteria may also contribute to its biotransformation. The aim of this study was to investigate the metabolism of IQ by the human intestinal microbiota. Following incubation of IQ (200 µM) under anoxic conditions with 100-fold dilutions of stools freshly collected from three healthy volunteers, we quantified residual IQ by high-pressure liquid chromatography (HPLC) analysis and characterized the production of IQ metabolites by in situ 1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis of crude incubation media. In addition, we looked for IQ-degrading bacteria by screening collection strains and by isolating new strains from the cecal contents of human-microbiota-associated rats gavaged with IQ on a regular basis. HPLC and 1H-NMR analyses showed that the three human microbiota degraded IQ with different efficiencies (range, 50 to 91% after 72 h of incubation) and converted it into a unique derivative, namely, 7-hydroxy-IQ. We found 10 bacterial strains that were able to perform this reaction: Bacteroides thetaiotaomicron (n = 2), Clostridium clostridiiforme (n = 3), Clostridium perfringens (n = 1), and Escherichia coli (n = 4). On the whole, our results indicate that bacteria belonging to the predominant communities of the human intestine are able to produce 7-hydroxy-IQ from IQ. They also suggest interindividual differences in the ability to perform this reaction. Whether it is a metabolic activation is still a matter of debate, since 7-hydroxy-IQ has been shown to be a direct-acting mutagen in the Ames assay but not carcinogenic in laboratory rodents.
C.H. and B.C. contributed equally.
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