title: Effect of cigarette smoking on urinary 2-hydroxypropylmercapturic acid, a metabolite of propylene oxide.
abstract: 2-Hydroxypropylmercapturic acid (2-HPMA) is a urinary biomarker of exposure to propylene oxide, a mutagen and carcinogen to which humans are exposed through inhalation of cigarette smoke as well as in certain environmental and occupational settings. 2-HPMA is the final product of a detoxification pathway in which propylene oxide is conjugated with glutathione, and the resulting conjugate is further metabolized and excreted. We have developed and validated a liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometric (LC-APCI-MS/MS) method for the rapid quantitation of 2-HPMA in human urine. The method was applied to an analysis of urine samples from 40 smokers and 40 nonsmokers as well as from a group of 15 subjects who quit smoking. The results demonstrate that smokers have significantly (P<0.001) higher levels of urinary 2-HPMA (median=480pmol/mg creatinine) than do nonsmokers (208pmol/mg). Similarly, subjects who quit smoking for four weeks exhibited a significant (P<0.001) 52% median decrease in urinary 2-HPMA upon cessation. Approximately 5% of all urine samples had unusually high levels of 2-HPMA (>10 times higher than the median), apparently unrelated to tobacco smoke exposure or available demographic data. The method presented here can be used to rapidly quantify an individual's exposure to propylene oxide via tobacco smoke or other sources.
authors.affiliation: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA. Electronic address: zarth002@umn.edu.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Zarth
authors.affiliation: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Carmella
authors.affiliation: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
authors.forename: Chap T
authors.initials: CT
authors.lastname: Le
authors.affiliation: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism / Q000652:urine*; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods; D004852:Epoxy Compounds / Q000378:metabolism*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012907:Smoking / Q000378:metabolism*; D016540:Smoking Cessation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D055815:Young Adult
chemical_list: D004852:Epoxy Compounds; D000111:Acetylcysteine; C009068:propylene oxide
keywords: Cigarette smoke; Mercapturic acid; Propylene oxide; Smoking cessation