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-pyri dyl)-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 5-3HNNK and individually incubated at 37°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.