Association between Glucuronidation Genotypes and Urinary NNAL Metabolic Phenotypes in Smokers.

ABSTRACT:

Background

The most abundant and potent carcinogenic tobacco-specific nitrosamine in tobacco and tobacco smoke is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In vivo, NNK is rapidly metabolized to both the (R)- and (S)-enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which possesses similar carcinogenic properties as NNK. The major detoxification pathway for both NNAL enantiomers is glucuronidation by UDP-glucuronosyltransferase (UGT) enzymes including UGT2B10 and UGT2B17. The goal of the present study was to directly examine the role of UGT genotypes on urinary levels of NNAL glucuronides in smokers.

Methods

NNAL-N-Gluc, (R)-NNAL-O-Gluc, (S)-NNAL-O-Gluc, and free NNAL were simultaneously and directly quantified in the urine of smokers by LC/MS

SUBMITTER: Chen G 

PROVIDER: S-EPMC5087993 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature