{'fraction_non_alphanumeric': 0.07037747920665387, 'fraction_numerical': 0.016634676903390915, 'mean_word_length': 4.924242424242424, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Stereochemistry of metabolites of a tobacco-specific lung carcinogen in smokers' urine.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific lung carcinogen, is believed to be important as a causative agent for lung cancer in smokers. NNK is extensively metabolized to its carbonyl reduction product 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which, in turn, can be glucuronidated, producing [4-methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic+ ++ acid (NNAL-Gluc). Metabolism of NNK to NNAL produces a chiral center. A recent study demonstrated that (R)-NNAL is more tumorigenic in mice than (S)-NNAL and that these enantiomers have substantially different metabolic pathways. Therefore, it is important to determine the stereochemistry of NNAL and NNAL-Gluc in smokers. In this study, we used chiral stationary phase-gas chromatography-nitrosamine-selective detection with confirmation by liquid chromatography-tandem mass spectrometry to determine the stereochemistry of NNAL and NNAL-Gluc in smokers' urine. The two methods agreed well. The results of analyses of urine samples from 30 smokers demonstrated that the enantiomeric distribution of NNAL in urine was 54% (R) and 46% (S) +/- 7.0 (SD), whereas the diastereomeric distribution of NNAL-Gluc was 68% (R) and 32% (S) +/- 8.1. These results conclusively demonstrate that both (R)- and (S)-NNAL are formed metabolically from NNK in smokers. These data are essential for furthering our understanding of the role of NNK as a cause of lung cancer in smokers.