Metabolism of 1-, 3-, and 6-nitrobenzo[a]pyrene by intestinal microflora.
The compounds 1-, 3-, and 6-nitrobenzo[a]pyrene (nitro-BaP) are environmental pollutants and have been shown to be potent bacterial mutagens. The anaerobic metabolism of these isomeric nitro-BaPs was investigated by the incubation of rat intestinal microflora with each isomer for 48 h. Aliquots were removed at several time intervals, extracted, fractionated by high-pressure liquid chromatography (HPLC), and the radioactivity determined. Metabolites were identified by comparison of their chromatographic, ultraviolet-visible absorption, and mass spectral properties with those of authentic standards. The order of the extent of nitroreduction for these isomers was 3-nitro-BaP greater than 6-nitro-BaP greater than 1-nitro-BaP. After 48 h of exposure, 84% of the added 3-nitro-BaP was present as 3-amino-BaP, 51% of the 6-nitro-BaP was metabolized to 6-amino-BaP, and 1-nitro-BaP was reduced to 1-amino-BaP (13%) and 1-nitro-BaP (4%). The order of the extent of microbial nitroreduction for these nitro-BaP isomers is different from the predictions based on electronic and steric hindrance effects. These results suggest that intestinal microflora nitroreductases exhibit a markedly high degree of substrate specificity toward nitro-BaPs that affects the extent of nitroreduction.
Richardson
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National Center for Toxicological Research, FDA, Jefferson, Arkansas 72079.
Fu
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Cerniglia
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D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D046508:Culture Techniques; D005260:Female; D007422:Intestines / Q000382:microbiology*; D013058:Mass Spectrometry; D051381:Rats; D014316:Tritium
D001580:Benzopyrenes; D014316:Tritium; C034699:6-nitrobenzo(a)pyrene; C042055:3-nitrobenzo(a)pyrene; C040217:1-nitrobenzo(a)pyrene