Metabolic activation of bladder procarcinogens, 2-aminofluorene, 4-aminobiphenyl, and benzidine by Pseudomonas aeruginosa and other human endogenous bacteria

Pseudomonas aeruginosa, an opportunistic pathogen of the human urinary tract, and other selected human endogenous bacteria were investigated for metabolic activation of the bladder procarcinogens, 2-aminofluorene (2-AF), 4-aminobiphenyl (4-AB), and benzidine (Bz). The cell-free extracts of Pseudomonas aeruginosa, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis, Proteus vulgaris, Staphylococcus epidermidis, Staphylococcus saprophyticus, Klebsiella pneumoniae, and intestinal anaerobes, Bacteroides fragilis, Clostridium perfringens, and Eubacterium aerofaciens produced increased histidine revertant frequencies with the tester strain Salmonella typhimurium TA98 in the Ames Salmonella mutagenicity assay. In addition, the cell-free extracts of Pseudomonas aeruginosa, Bacteroides fragilis, and Eubacterium aerofaciens each showed the presence of a cytochrome P450 absorption peak in the carbon monoxide (CO) difference spectrum. This was not demonstratable for the other bacteria. Our findings indicate that human endogenous bacteria, which are opportunistic pathogens of the urinary bladder, can metabolically activate the bladder procarcinogens 2-AF, 4-AB, and Bz into mutagens. The metabolic activation by Pseudomonas aeruginosa, Bacteroides fragilis, and Eubacterium aerofaciens is mediated by a cytochrome P450 enzyme. For those organisms that induced metabolic activation but did not show a P450 absorption peak with the cell-free extracts, other oxidative enzymes may be involved.