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
Year: 2007
Type: article
Study design: Observational Study
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.
Source: Chemical Research in Toxicology
DOI: 10.1021/tx700075y
Institution: University of Minnesota
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2070453504