Mutagenic activation of biliary metabolites of benzo(a)pyrene by  -glucuronidase-positive bacteria in human faeces

Abstract

Summary. Human faeces hydrolysed synthetic P-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 P-glucuronidase activity isolated from fresh human faeces were identified as species of Bacteroides, Peptostreptococcus, Fusobacterium, Propionibacterium, Clostridium, Eubacteriurn and Bijidobacterium. They were classified into two groups according to their activity against two synthetic P-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 P-glucuronidase-positive bacteria increased the mutagenicity of metabolites of benzo(a)pyrene, as did faecal extracts, but extracts of P-glucuronidasenegative bacteria did not. D-Saccharic acid-1,4-1actone inhibited the increase in mutagenicity produced by the faecal extracts and extracts of P-glucuronidase-positive bacteria except for Peptostreptococcus strains 204 and 952. These results indicate that some intestinal bacteria have P-glucuronidases heterogenous in substrate specificity and that they may be involved in mutagenicity of benzo(a)pyrene in the intestinal tract.

Anticarcinogenic Factors in Plant Foods: A New Class of Nutrients?

“…For instance, when potentially carcinogenic compounds are detoxified by UDPGT (Dutton, 1980) . /I-Glucuronidase activity has been implicated in the activation of benzo(a)pyrene and 1,2-dimethylhydrazine conjugates in the colon (Nanno et al 1986;Mallett & Rowland, 1990). It has been demonstrated that the yield of colorectal tumours is lower in germ free rats exposed to 1 ,Zdimethylhydrazine than in similarly treated conventional rats (Reddy et al 1974) and that a /I-glucuronidase inhibitor can protect rats with a conventional flora from the induction of tumours by azoxymethane, a metabolite of 1 ,Zdimethylhydrazine (Takada et al 1982).…”

The effect of doxorubicin on rats that received toxic and carcinogenic benzo(a)pyrene.

“…In the group of PAHs, B(a)P has the highest potential to cause cancer [2,4,8,9]. Furthermore, B(a)P has also mutagenic and teratogenic effects [2,6,[10][11][12]. It transforms into (+)-BP-7-8-oxide by the monooxigenase enzyme, into (-)-trans-BP-7,8-dihydrodiol by the epoxide hydrolase enzyme and into (+)-anti-BP-7,8-diol-9,10-epoxide by the monooxigenase enzyme [1,5].…”

Bacterial Enzymes: Their Role in the Formation of Mutagens and Carcinogens in the Intestine

“…Po lar conjugates, including the glucuronide, are excreted into bile after the administration of BaP to rodents [15] and hydrolyzed to BaP diols and BaP by intestinal microorganisms. These products are directly mutagenic in bacterial test systems [16] and bind to DNA in vitro [17], whereas hepatic conjugates of BaP show no genotoxic activity when P-gluc uronidase activity is absent [18]. These ob servations suggest that bacterial products formed from BaP in the large intestine are potential candidates as initiators of the car cinogenic transformation of mucosal cells.…”