Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Feasibility of using urinary N7-(2-carbamoyl-2-hydroxyethyl) Guanine as a biomarker for acrylamide exposed workers


Acrylamide (AA), a probable human carcinogen, is a widely-used industrial chemical but is also present in tobacco smoke and carbohydrate-rich foods processed at high temperatures. AA is metabolized to glycidamide (GA) to cause the formation of DNA adducts. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct induced by GA, was recently detected in urine of smokers and non-smokers. In this study, we assessed the variability of AA exposure and biomarkers of AA exposure in urine samples repeatedly collected from AA-exposed workers and explored the half-life of N7-GAG. A total of 8 AA-exposed workers and 36 non-exposed workers were recruited. Pre-shift and post-shift urine samples were collected from the exposed group in parallel with personal sampling for eight consecutive days and from the control group on day 1 of the study. Urinary N7-GAG and the mercapturic acids of AA and GA, namely N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) were analyzed using on-line solid phase extraction-liquid chromatography-electrospray ionization/tandem mass spectrometry methods. We found that N7-GAG levels in urine were significantly higher in exposed workers than in controls and that N7-GAG level correlated positively with AAMA and GAMA levels. Results from this study showed that AAMA and GAMA possibly remain the more preferred biomarkers of AA exposure and that N7-GAG levels could be elevated by occupational exposures to AA and serve as a biomarker of AA-induced genotoxicity for epidemiological studies.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    IARC. IARC monographs on the evaluation of carcinogen risk to humans: some industrial chemicals. Lyon: IARC; 1994.

  2. 2.

    NSC. Chemical backgrounders index: acrylamide. 2006.

  3. 3.

    U.S. EPA (2010). Toxicological review of acrylamide (CAS No. 79-06-1) in support of summary information on the Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. EPA/635/R-07/009F.

  4. 4.

    Tareke E, Rydberg P, Karlsson P, Eriksson S, Tornqvist M. Analysis of Acrylamide, a Carcinogen Formed in Heated Foodstuffs. J Agric Food Chem. 2002;50:4998–5006.

    CAS  Article  Google Scholar 

  5. 5.

    Joint FAO/WHO Expert Committee on Food Additives (2005 : Rome, Italy) Evaluation of certain food contaminants : sixty-fourth report of the Joint FAO/WHO Expert Committee on Food Additives.(WHO technical report series; 930) No. 930, 2006. p 7-17.

  6. 6.

    Smith CJ, Perfetti TA, Rumple MA, Rodgman A, Doolittle DJ. “IARC Group 2A Carcinogens” reported in cigarette mainstream smoke. Food Chem Toxicol. 2000;38:371–83.

    CAS  Article  Google Scholar 

  7. 7.

    Bull RJ, Robinson M, Laurie RD, Stoner GD, Greisiger E, Meier JR, et al. Carcinogenic effects of acrylamide in Sencar and A/J mice. Cancer Res. 1984;44:107–11.

    CAS  PubMed  Google Scholar 

  8. 8.

    Johnson KA, Gorzinski SJ, Bodner KM, Campbell RA, Wolf CH, Friedman MA, et al. Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicol Appl Pharmacol. 1986;85:154–68.

    CAS  Article  Google Scholar 

  9. 9.

    Friedman MA, Dulak LH, Stedham MA. A lifetime oncogenicity study in rats with acrylamide. Toxicol Sci. 1995;27:95–105.

    CAS  Article  Google Scholar 

  10. 10.

    Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PAA. Prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer. Cancer Epidemiol Biomark Prev. 2007;16:2304–13.

    CAS  Article  Google Scholar 

  11. 11.

    Hogervorst JGF, Baars BJ, Schouten LJ, Konings EJM, Goldbohm RA, van den Brandt PA. The carcinogenicity of dietary acrylamide intake: A comparative discussion of epidemiological and experimental animal research. Crit Rev Toxicol. 2010;40:485–512.

    CAS  Article  Google Scholar 

  12. 12.

    Sumner SC, Fennell TR, Moore TA, Chanas B, Gonzalez F, Ghanayem BI. Role of cytochrome P450 2E1 in the metabolism of acrylamide and acrylonitrile in mice. Chem Res Toxicol. 1999;12:1110–6.

    CAS  Article  Google Scholar 

  13. 13.

    Ghanayem BI, McDaniel LP, Churchwell MI, Twaddle NC, Snyder R, Fennell TR, et al. Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts. Toxicol Sci. 2005;88:311–8.

    CAS  Article  Google Scholar 

  14. 14.

    Settels E, Bernauer U, Palavinskas R, Klaffke HS, Gundert-Remy U, Appel KE. Human CYP2E1 mediates the formation of glycidamide from acrylamide. Arch Toxicol. 2008;82:717–27.

    CAS  Article  Google Scholar 

  15. 15.

    Sumner SC, MacNeela JP, Fennell TR. Characterization and quantitation of urinary metabolites of [1,2,3-13C]acrylamide in rats and mice using 13C nuclear magnetic resonance spectroscopy. Chem Res Toxicol. 1992;5:81–9.

    CAS  Article  Google Scholar 

  16. 16.

    Sumner SC, Selvaraj L, Nauhaus SK, Fennell TR. Urinary metabolites from F344 rats and B6C3F1 mice coadministered acrylamide and acrylonitrile for 1 or 5 days. Chem Res Toxicol. 1997;10:1152–60.

    CAS  Article  Google Scholar 

  17. 17.

    Boettcher MI, Schettgen T, Kutting B, Pischetsrieder M, Angerer J. Mercapturic acids of acrylamide and glycidamide as biomarkers of the internal exposure to acrylamide in the general population. Mutat Res. 2005;580:167–76.

    CAS  Article  Google Scholar 

  18. 18.

    Huang CCJ, Li CM, Wu CF, Jao SP, Wu KY. Analysis of urinary N-acetyl-S-(propionamide)-cysteine as a biomarker for the assessment of acrylamide exposure in smokers. Environ Res. 2007;104:346–51.

    CAS  Article  Google Scholar 

  19. 19.

    Kopp EK, Sieber M, Kellert M, Dekant W. Rapid and sensitive HILIC-ESI-MS/MS quantitation of polar metabolites of acrylamide in human urine using column switching with an online trap column. J Agric Food Chem. 2008;56:9828–34.

    CAS  Article  Google Scholar 

  20. 20.

    Huang YF, Wu KY, Liou SH, Uang SN, Chen CC, Shih WC, et al. Biological monitoring for occupational acrylamide exposure from acrylamide production workers. Int Arch Occup Environ Health. 2010;84:303–13.

    Article  Google Scholar 

  21. 21.

    Gamboa da Costa, G, Churchwell, MI., Hamilton, LP, Von Tungeln, LS, Beland, FA, Marques, MM, Doerge, DR. DNA adduct formation from acrylamide via conversion to glycidamide in adult and neonatal mice. Chem Res Toxicol. 2003;16:1328–37.

  22. 22.

    Segerback D, Calleman CJ, Schroeder JL, Costa LG, Faustman EM. Formation of N-7-(2-carbamoyl-2-hydroxyethyl)guanine in DNA of the mouse and the rat following intraperitoneal administration of [14C]acrylamide. Carcinogenesis. 1995;16:1161–5.

    CAS  Article  Google Scholar 

  23. 23.

    Doerge DR, Gamboa da Costa G, McDaniel LP, Churchwell MI, Twaddle NC, Beland FA. DNA adducts derived from administration of acrylamide and glycidamide to mice and rats. Mutat Res/Genet Toxicol Environ Mutagen. 2005;580:131–41.

    CAS  Article  Google Scholar 

  24. 24.

    Koyama N, Yasui M, Kimura A, Takami S, Suzuki T, Masumura K, et al. Acrylamide genotoxicity in young versus adult gpt delta male rats. Mutagenesis. 2011;26:545–9.

    CAS  Article  Google Scholar 

  25. 25.

    Watzek N, Bohm N, Feld J, Scherbl D, Berger F, Merz KH, et al. N7-glycidamide-guanine DNA adduct formation by orally ingested acrylamide in rats: a dose-response study encompassing human diet-related exposure levels. Chem Res Toxicol. 2012;25:381–90.

    CAS  Article  Google Scholar 

  26. 26.

    Huang C-CJ, Wu C-F, Shih W-C, Luo Y-S, Chen M-F, Li C-M, et al. Potential association of urinary N7-(2-carbamoyl-2-hydroxyethyl) guanine with dietary acrylamide intake of smokers and nonsmokers. Chem Res Toxicol. 2015;28:43–50.

    CAS  Article  Google Scholar 

  27. 27.

    Farmer PB. DNA and protein adducts as markers of genotoxicity. Toxicol Lett. 2004;149:3–9.

    CAS  Article  Google Scholar 

  28. 28.

    Boysen G, Pachkowski BF, Nakamura J, Swenberg JA. The formation and biological significance of N7-guanine adducts. Mutat Res/Genet Toxicol Environ Mutagen. 2009;678:76–94.

    CAS  Article  Google Scholar 

  29. 29.

    Wu KY, Chiang SY, Shih WC, Huang CCJ, Chen MF, Swenberg JA. The application of mass spectrometry in molecular dosimetry: ethylene oxide as an example. Mass Spectrom Rev. 2011.

    Article  PubMed  Google Scholar 

  30. 30.

    Wu KY, Huang YF, Chen MF, Shih Ts, Uang SN, Mao IF et al. Exposure assessment of airborne acrylamide for occupationally exposed workers by using an isotope-dilution gas chromatography coupled with mass spectrometry. Ann Occup Hyg. 2010;54:575–83.

  31. 31.

    Jaffe M. Uber den niederschlag, welchen pikriksaure in normalen harn erzeugt und uber eine neue reaction des kreatinins. Z Physiol Chem. 1886;10:391.

    Google Scholar 

  32. 32.

    Rappaport S, Lyles R, Kupper LAN. Exposure—assessment strategy accounting for within-and between-worker sources of variability. Ann Occup Hyg. 1995;39:469–95.

    CAS  Article  Google Scholar 

  33. 33.

    Lin YS, Kupper LL, Rappaport SM. Air samples versus biomarkers for epidemiology. Occup Environ Med. 2005;62:750–60.

    CAS  Article  Google Scholar 

  34. 34.

    Maniere I, Godard T, Doerge DR, Churchwell MI, Guffroy M, Laurentie M, et al. DNA damage and DNA adduct formation in rat tissues following oral administration of acrylamide. Mutat Res/Genet Toxicol Environ Mutagen. 2005;580:119–29.

    CAS  Article  Google Scholar 

  35. 35.

    Nixon BJ, Stanger SJ, Nixon B, Roman SD. Chronic exposure to acrylamide induces DNA damage in male germ cells of mice. Toxicol Sci. 2012;129:135–45.

    CAS  Article  Google Scholar 

  36. 36.

    Watzek N, Scherbl D, Schug M, Hengstler J, Baum M, Habermeyer M, et al. Toxicokinetics of acrylamide in primary rat hepatocytes: coupling to glutathione is faster than conversion to glycidamide. Arch Toxicol. 2013;87:1545–56.

    CAS  Article  Google Scholar 

  37. 37.

    Li CM, Hu CW, Wu KY. Quantification of urinary N-acetyl-S- (propionamide)cysteine using an on-line clean-up system coupled with liquid chromatography/tandem mass spectrometry. J Mass Spectrom. 2005;40:511–15.

    Article  Google Scholar 

  38. 38.

    Urban M, Kavvadias D, Riedel K, Scherer G, Tricker AR. Urinary mercapturic acids and a hemoglobin adduct for the dosimetry of acrylamide exposure in smokers and nonsmokers. Inhal Toxicol. 2006;18:831–9.

    CAS  Article  Google Scholar 

  39. 39.

    Bjellaas T, Stolen LH, Haugen M, Paulsen JE, Alexander J, Lundanes E, et al. Urinary acrylamide metabolites as biomarkers for short-term dietary exposure to acrylamide. Food Chem Toxicol. 2007;45:1020–6.

    CAS  Article  Google Scholar 

  40. 40.

    Hartmann EC, Boettcher MI, Schettgen T, Fromme H, Drexler H, Angerer J. Hemoglobin adducts and mercapturic acid excretion of acrylamide and glycidamide in one study population. J Agric Food Chem. 2008;56:6061–8.

    CAS  Article  Google Scholar 

  41. 41.

    Fennell TR, Sumner SCJ, Snyder RW, Burgess J, Spicer R, Bridson WE, et al. Metabolism and hemoglobin adduct formation of acrylamide in humans. Toxicol Sci. 2005;85:447–59.

    CAS  Article  Google Scholar 

  42. 42.

    Fuhr U, Boettcher MI, Kinzig-Schippers M, Weyer A, Jetter A, Lazar A, et al. Toxicokinetics of acrylamide in humans after ingestion of a defined dose in a test meal to improve risk assessment for acrylamide carcinogenicity. cancer epidemiology biomarkers. Prevention. 2006;15:266–71.

    CAS  Google Scholar 

  43. 43.

    Loeb LA, Preston BD. Mutagenesis by apurinic/apyrimidinic sites. Annu Rev Genet. 1986;20:201–30.

    CAS  Article  Google Scholar 

  44. 44.

    Besaratinia A, Pfeifer GP. Genotoxicity of acrylamide and glycidamide. J Natl Cancer Inst. 2004;96:1023–9.

    CAS  Article  Google Scholar 

  45. 45.

    Manjanatha MG, Aidoo A, Shelton SD, Bishop ME, McDaniel LP, Lyn-Cook LE, et al. Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice. Environ Mol Mutagen. 2006;47:6–17.

    CAS  Article  Google Scholar 

Download references


This research was finically supported by a grant from the National Health Research Institute (EO-095-PP-02), a grant from the National Science Council of the Republic of China, Taiwan (MOST 95–2314-B-400-004-MY3), and a grant from Institute of Occupational Safety and Health (IOSH95-A319), Taiwan. We acknowledge the cooperation of the staff in the IOSH and our study participant.

Author information



Corresponding author

Correspondence to Kuen-Yuh Wu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huang, YF., Huang, CC.J., Lu, C.A. et al. Feasibility of using urinary N7-(2-carbamoyl-2-hydroxyethyl) Guanine as a biomarker for acrylamide exposed workers. J Expo Sci Environ Epidemiol 28, 589–598 (2018).

Download citation


  • Acrylamide
  • N7-(2-carbamoyl-2-hydroxyethyl) guanine
  • Glycidamide
  • Biomarker
  • Occupatonal exposure


Quick links