Potential association of urinary N7-(2-carbamoyl-2-hydroxyethyl) guanine with dietary acrylamide intake of smokers and nonsmokers

Chih Chun Jean Huang, Chia Fang Wu, Wei Chung Shih, Yu Syuan Luo, Ming Feng Chen, Chien Ming Li, Saou Hsing Liou, Wen-Sheng Chung, Su Yin Chiang*, Kuen Yuh Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 C 3 -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.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalChemical Research in Toxicology
Issue number1
StatePublished - 20 Jan 2015


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