Potential Association of Urinary N7-(2-Carbamoyl-2-hydroxyethyl) Guanine with Dietary Acrylamide Intake of Smokers and Nonsmokers
Autor: | Chia Fang Wu, Ming Feng Chen, Su Yin Chiang, Yu-Syuan Luo, Kuen-Yuh Wu, Saou-Hsing Liou, Chien Ming Li, Chih Chun Jean Huang, Wen-Sheng Chung, Wei Chung Shih |
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Rok vydání: | 2014 |
Předmět: |
Adult
Guanine Metabolite Urine Toxicology medicine.disease_cause chemistry.chemical_compound Young Adult DNA adduct medicine Humans Cotinine Carcinogen Acrylamide Smoking General Medicine Environmental Exposure Acetylcysteine Diet chemistry Biochemistry Carcinogens Depurination Genotoxicity Biomarkers |
Zdroj: | Chemical research in toxicology. 28(1) |
ISSN: | 1520-5010 |
Popis: | Acrylamide (AA), a rodent carcinogen, is widely used in industry and present in cigarette smoke as well as in foods processed at high temperatures. The metabolic activation of AA to glycidamide (GA) could be critical for AA carcinogenicity since GA causes DNA adduct formation in vivo. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct of AA, is subjected to spontaneous and enzymatic depurination and excreted through urine. Urinary N7-GAG analysis can confirm AA genotoxicity and identify active species of AA metabolites in humans, thereby serving as a risk-associated biomarker for molecular epidemiology studies. This study aimed to develop an isotope-dilution solid-phase extraction liquid chromatography tandem mass spectrometry method to comparatively analyze urinary N7-GAG levels in nonsmokers and smokers. Urinary N-acetyl-S-(propionamide)-cysteine (AAMA), a metabolite of AA, was also analyzed as a biomarker for current AA exposure. Urinary N7-GAG was quantified by monitoring m/z 239 → 152 for N7-GAG and m/z 242 → 152 for (13)C3-labeled N7-GAG under positive electron spray ionization and multiple reaction mode. The median urinary N7-GAG level was 0.93 μg/g creatinine in nonsmokers (n = 33) and 1.41 μg/g creatinine in smokers (n = 30). Multiple linear regression analysis of data revealed that N7-GAG levels were only significantly associated with AAMA levels. These results demonstrate that urinary N7-GAG of nonsmokers and smokers is significantly associated with a very low level of dietary AA intake, assessed by analyzing urinary AAMA. |
Databáze: | OpenAIRE |
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