Mutagenic activation of biliary metabolites of benzo(a)pyrene by beta-glucuronidase-positive bacteria in human faeces.
Human faeces hydrolysed synthetic beta-D-glucuronides of both p-nitrophenol and phenolphthalein. The origin of this activity in faeces was localised in the bacterial pellet fraction after centrifugation. Ninety-seven bacterial strains with beta-glucuronidase activity isolated from fresh human faeces were identified as species of Bacteroides, Peptostreptococcus, Fusobacterium, Propionibacterium, Clostridium, Eubacterium and Bifidobacterium. They were classified into two groups according to their activity against two synthetic beta-D-glucuronides. One group hydrolysed p-nitrophenyl glucuronide and phenolphthalein glucuronide to the same extent and the other hydrolysed p-nitrophenyl glucuronide much more strongly than phenolphthalein glucuronide. The bile of rats given benzo(a)pyrene by mouth was tested for mutagenicity in the presence and absence of cell-free extracts of human faeces and bacteria. Extracts of beta-glucuronidase-positive bacteria increased the mutagenicity of metabolites of benzo(a)pyrene, as did faecal extracts, but extracts of beta-glucuronidase-negative bacteria did not. D-Saccharic acid-1,4-lactone inhibited the increase in mutagenicity produced by the faecal extracts and extracts of beta-glucuronidase-positive bacteria except for Peptostreptococcus strains 204 and 952. These results indicate that some intestinal bacteria have beta-glucuronidases heterogenous in substrate specificity and that they may be involved in mutagenicity of benzo(a)pyrene in the intestinal tract.
D000328:Adult; D000818:Animals; D001419:Bacteria / Q000201:enzymology* / Q000378:metabolism; D001438:Bacteroidaceae / Q000201:enzymology / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D005243:Feces / Q000382:microbiology*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D010462:Peptostreptococcus / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D009153:Mutagens; D001564:Benzo(a)pyrene; D005966:Glucuronidase