Acrylamide, a chemical widely used in industry and present in cigarette smoke, is a known rodent carcinogen and can be spontaneously formed in foods processed at high temperatures. DNA damage caused by acrylamide, N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), was found to be significantly associated with acrylamide metabolite in the urine of both smokers and nonsmokers, according to a study by researchers from National Taiwan University (NTU), National Health Research Institutes, and China Medical University. This study has been published in the January 2015 issue of Chemical Research in Toxicology.
[Photo: Dr. Kuen-Yuh Wu]
The potential health effects due to acrylamide intake through daily food consumption have been of great concerns. N7-GAG is formed by the reaction between guanine of DNA and acrylamide active metabolite, glycidamide (GA). N7-GAG can be spontaneously and enzymatically depurinated from DNA backbone to form abasic site and excreted through urine. “The abasic site may cause mutation and lead to cancer development if not repaired prior to cell proliferation,” said Professor Kuen-Yuh Wu of NTU, the senior author of the article. N7-GAG showed dose-dependent increases with acrylamide doses in animal studies.
The research team was led by Professor Kuen-Yuh Wu in the College of Public Health of NTU. An isotope-dilution liquid chromatography tandem mass spectrometry method was first developed by Dr. Chih-Chun Huang, a former post-doctor at National Health Research Institutes to analyze N7-GAG in urine samples collected from 33 self-reported nonsmokers and smokers, respectiveky, with no history of occupational exposures to acrylamide. Urinary N7-GAG was quantified by monitoring m/z 239®152 for N7-GAG and m/z 242®152 for 13C3-labelled N7-GAG under positive electron spray ionization and multiple reaction mode. Background information of the study subjects was collected with questionnaires. Urinary cotinine and N-acetyl-S-(propionamide)-cysteine (AAMA), a metabolite of acrylamide, was also analyzed as a biomarker for smoking status and current acrylamide exposure.
The median urinary N7-GAG level was 0.93 mg/g creatinine in non-smokers (n=33) and 1.41 mg/g creatinine in smokers (n=30). Multiple linear regression analysis of data revealed that N7-GAG levels were only significantly associated with urinary AAMA levels. According to Professor Wu, “These results first demonstrate that urinary N7-GAG of both non-smokers and smokers is significantly associated with very low level of dietary acrylamide intake and suggest that low levels of acrylamide exposures through food consumption may cause acrylamide-specific DNA damage.” Furthermore, continued Professor Wu, “Urinary N7-GAG analysis can confirm acrylamide genotoxicity and identify active species of acrylamide metabolites in humans, thereby serving as a risk-associated biomarker for future molecular epidemiology studies.”