Quantitation of Acrolein-Derived (3-Hydroxypropyl)mercapturic Acid in Human Urine by Liquid Chromatography-Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry: Effects of Cigarette Smoki
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- 作者：Steven G. Carmella ; Menglan Chen ; Yan Zhang ; Siyi Zhang ; Dorothy K. Hatsukami ; Stephen S. Hecht
- 刊名：Chemical Research in Toxicology
- 出版年：2007
- 出版时间：July 2007
- 年：2007
- 卷：20
- 期：7
- 页码：986 - 990
- 全文大小：68K
- 年卷期：v.20,no.7(July 2007)
- ISSN：1520-5010
文摘
Recently published data suggest that acrolein (1), a toxic but weakly carcinogenic constituent of cigarettesmoke, may be involved as a causative factor for the mutations frequently observed in the p53 tumorsuppressor gene in lung cancer in smokers. Biomarkers are needed to further assess the possible relationshipbetween 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 methodemploys [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 preciseand required only 0.1 mL of urine. Median levels of 3-HPMA were significantly higher (2900 pmol/mgof 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 4week smoking cessation period. There was a significant 78% decrease in median levels of urinary 3-HPMAafter 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 wasa significant inverse relationship between urinary 3-HPMA and 
-hydroxy-PdG (3) but not 
-hydroxy-PdG (4) or total adduct levels. The results of this study clearly demonstrate that acrolein uptake in smokersis significantly higher than in nonsmokers and underline the need for further investigation of the possiblerelationship of acrolein uptake to lung cancer.
-hydroxy-PdG (3) but not -hydroxy-PdG (4) or total adduct levels. The results of this study clearly demonstrate that acrolein uptake in smokersis significantly higher than in nonsmokers and underline the need for further investigation of the possiblerelationship of acrolein uptake to lung cancer.