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. 2007 Jul;20(7):986-90.
doi: 10.1021/tx700075y. Epub 2007 Jun 9.

Quantitation of acrolein-derived (3-hydroxypropyl)mercapturic acid in human urine by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry: effects of cigarette smoking

Steven G Carmella  1 , Menglan Chen, Yan Zhang, Siyi Zhang, Dorothy K Hatsukami, Stephen S Hecht
Affiliations

Quantitation of acrolein-derived (3-hydroxypropyl)mercapturic acid in human urine by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry: effects of cigarette smoking

Steven G Carmella et al. Chem Res Toxicol. 2007 Jul.

Abstract

Recently published data suggest that acrolein (1), a toxic but weakly carcinogenic constituent of cigarette smoke, may be involved as a causative factor for the mutations frequently observed in the p53 tumor suppressor gene in lung cancer in smokers. Biomarkers are needed to further assess the possible relationship between acrolein uptake and cancer. In this study, we analyzed (3-hydroxypropyl)mercapturic acid (3-HPMA, 2) in human urine. 3-HPMA is a major metabolite of acrolein in laboratory animals. The method employs [13C3]3-HPMA as an internal standard, with analysis and quantitation by LC-APCI-MS/MS-SRM. Clean, readily quantifiable chromatograms were obtained. The method was accurate and precise and required only 0.1 mL of urine. Median levels of 3-HPMA were significantly higher (2900 pmol/mg of creatinine, N=35) in smokers than in nonsmokers (683 pmol/mg of creatinine, N=21) (P=0.0002). The effect of smoking was further assessed by determining the levels of 3-HPMA before and after a 4 week smoking cessation period. There was a significant 78% decrease in median levels of urinary 3-HPMA after cessation (P<0.0001). The relationship between the levels of urinary 3-HPMA and those of acrolein-derived 1,N2-propanodeoxyguanosine (PdG) adducts in lung was investigated in 14 smokers. There was a significant inverse relationship between urinary 3-HPMA and alpha-hydroxy-PdG (3) but not gamma-hydroxy-PdG (4) or total adduct levels. The results of this study clearly demonstrate that acrolein uptake in smokers is significantly higher than in nonsmokers and underline the need for further investigation of the possible relationship of acrolein uptake to lung cancer.

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Figures

Figure 1
Figure 1
Chromatograms obtained upon LC-APCI-MS/MS-SRM analysis of a smoker’s urine for 3-HPMA. Top panel, the peak for 3-HPMA elutes at 8.89 min. Bottom panel, the peak for the internal standard, [13C3]3-HPMA also elutes at 8.89 min.
Figure 2
Figure 2
Relationship between added and measured 3-HPMA in urine. 3-HPMA was added to a non-smoker’s urine and it was analyzed by the method described in the text.
Figure 3
Figure 3
Levels of 3-HPMA in the urine of 35 smokers and 21 non-smokers. Boxes represent 25th and 75th percentile, lines represent 10th and 90th percentile, and dots represent outliers. The difference between the median levels in smokers and non-smokers was significant (P = 0.0002)
Figure 4
Figure 4
Levels of 3-HPMA in the urine of smokers who abstained from smoking for 4 weeks. Solid bars represent levels in subjects at baseline, while still smoking. Open bars represent levels after these smokers had abstained.
See this image and copyright information in PMC

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