Bacterial reduction of N-oxides of tobacco-specific nitrosamines (TSNA)

1. Contrary to established metabolic pattern, a recent investigation of NNK metabolism produced in rat urine higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) than their N-oxides, suggesting that reconversion of N-oxides could occur after urine formation. 2. To verify the possible role of bacteria in the reduction of NNK-N-oxide and NNAL-N-oxide to their respective parent compounds, NNK and NNAL, in smokers with urinary tract infection (UTI), the N-oxides were isolated from the urine of rats treated with [5-3H]NNK and individually incubated at 37 degrees C with ten bacterial species in sterile human urine under different pH regimens. After incubation with the bacteria, aliquots of culture media were analyzed by high pressure liquid chromatography (HPLC) with radiochemical detection. 3. Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Proteus mirabilis possessed varying capacity to regenerate NNK and NNAL from their N-oxides while others showed no detectable reductive capability within 24 h. 4. This result constitutes the first experimental evidence that in tobacco users with concomitant UTI, bacterial regeneration of the procarcinogenic NNK and NNAL from their N-oxides could occur in the bladder leading to increased carcinogen burden in these individuals.