SpringerLink
Log in

Determination of Metabolites of Selected Thermally Treated Food-Derived Mutagens and Carcinogens in Biological Material

  • Living reference work entry
  • First Online:
Handbook of Bioanalytics

  • 17 Accesses

Abstract

Thermal processing of food can lead to the formation of compounds harmful to human health. These include heterocyclic aromatic amines (HAAs) formed in meat products and acrylamide (AAM) mainly formed in food with a high-starch content. These compounds show genotoxic, carcinogenic, and neurotoxic effects. This review of published studies provides a brief discussion of the routes of metabolic activation and detoxification of heterocyclic amines and acrylamide and presents to date results of research of exposure biomarkers quest, especially long-term biomarkers which could be used in molecular epidemiology studies.

The methods used to isolate heterocyclic amines, acrylamide, and their metabolites from biological samples (urine, blood, tissues, hair) depend on both the composition of the samples matrix and the type of compounds to be determined. This chapter describes procedures used for isolation and determination of HAA and acrylamide and their metabolites in urine, metabolites’ adducts with blood proteins (HAA with albumin and acrylamide with hemoglobin), as well as adducts of HAA metabolites with DNA in tissues and saliva. Nowadays, by using the latest technical solutions for instrumental analysis, including ultra-performance liquid chromatography (UPLC) and nano-UPLC coupled with high-resolution mass spectrometry, it is possible to assess the exposure to food-derived HAAs by their determination in hair at the level of tens pg/g. No biomarker of the exposure to acrylamide has been preferred so far, although it is possible to determine its metabolites in urine and adducts with hemoglobin in blood.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

Abbreviations

dG:

Deoxyguanosine

GC-MS/NCI:

Gas chromatography, electron-capture negative-ion chemical ionization mass spectrometry.

HPLC-DAD:

High-performance liquid chromatography with a diode-array detector.

LC-ESI/MS2:

Liquid chromatography-electrospray ionization-tandem mass spectrometry.

LC-ESI/MSn:

Liquid chromatography-electrospray ionization/multistage tandem mass spectrometry.

LC-MS2:

Liquid chromatography-tandem mass spectrometry.

Nano-LC-Orbitrap-MSn:

Nanoflow liquid chromatography-Orbitrap/multistage mass spectrometry.

SAX:

Strong anion-exchange phase.

SPE:

Solid-phase extraction.

SPE-C18:

SPE on a reversed phase (C18).

SPE-CX:

SPE on mixed-mode cation-exchange phase (silica or polymeric reversed-phase materials with an ion-exchange group, e.g., -SO3, bonded to it).

SPE-HCX:

SPE on mixed mode non-polar and strong cation-exchange phase.

SPE-HRP:

SPE on phase modified enzymatically with horseradish peroxidase.

SPE-MCX:

SPE on mixed-mode cation-exchange and reversed phase.

SPE-SCX:

SPE on a strong cation-exchange phase (e.g., silica gel modified with benzenesulfonic acid groups).

SPE-WAX:

SPE on weak anion-exchange phase.

UPLC-ESI/MSn:

Ultraperformance liquid chromatography-electrospray ionization/multistage mass spectrometry.

UPLC/ion trap-Orbitrap-MS3:

Ultraperformance liquid chromatography-Orbitrap high-resolution multistage mass spectrometry.

References

  1. Koszucka, A., & Nowak, A. (2018). Thermal processing food-related toxicants: A review. Critical Reviews in Food Science and Nutrition, 12, 1–18.

    Google Scholar 

  2. Turesky, R. J. (2018). Mechanistic evidence for red meat and processed meat intake and cancer risk: A follow-up on the International Agency for Research on Cancer evaluation of 2015. Chimia, 72, 718–724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2018). Red meat and processed meat. IARC Monographs, 114, Lyon.

    Google Scholar 

  4. Gibis, M. (2016). Heterocyclic aromatic amines in cooked meat products: Causes, formation, occurrence, and risk assessment. Comprehensive Reviews in Food Science and Food Safety, 15, 269–302.

    Article  CAS  PubMed  Google Scholar 

  5. Sugimura, T., Wakabayashi, K., Nakagama, H., & Nagao, M. (2004). Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. Cancer Science, 95, 290–299.

    Article  CAS  PubMed  Google Scholar 

  6. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. (1993). Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. IARC Monographs, 56, Lyon.

    Google Scholar 

  7. Skog, K. I., Johansson, M. A. E., & Jägerstad, M. I. (1998). Carcinogenic heterocyclic amines in model systems and cooked foods: A review on formation, occurrence and intake. Food and Chemical Toxicology, 36, 879–896.

    Article  CAS  PubMed  Google Scholar 

  8. Murkovic, M. (2007). Analysis of heterocyclic aromatic amines. Analytical and Bioanalytical Chemistry, 389, 139–146.

    Article  CAS  PubMed  Google Scholar 

  9. O’Gorman, A., Gibbons, H., & Brennan, L. (2013). Metabolomics in the identification of biomarkers of dietary intake. Computational and Structural Biotechnology Journal, 4, e201301004. https://doi.org/10.5936/csbj.201301004

  10. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. (2012). Chemical Agents and Related Occupations. A review of human carcinogens. IARC Monographs, 100F, Lyon.

    Google Scholar 

  11. **ao, S., Guo, J., Yun, B. H., et al. (2016). Biomonitoring DNA adducts of cooked meat carcinogens in human prostate by nano liquid chromatography-high resolution tandem mass spectrometry: Identification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine DNA Adduct. Analytical Chemistry, 88, 12508–12515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bellamri, M., **ao, S., Murugan, P., et al. (2018). Metabolic activation of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in human prostate. Toxicological Sciences, 163, 543–556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cooper, K. M., Brennan, S. F., Woodside, J. V., et al. (2016). Acid-labile protein-adducted heterocyclic aromatic amines in human blood are not viable biomarkers of dietary exposure: A systematic study. Food and Chemical Toxicology, 91, 100–107.

    Article  CAS  PubMed  Google Scholar 

  14. Ushiyama, H., Wakabayashi, K., Hirose, M., et al. (1991). Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation. Carcinogenesis, 12, 1417–1422.

    Article  CAS  PubMed  Google Scholar 

  15. Bellamri, M., Wang, Y., Yonemori, K., et al. (2018). Biomonitoring an albumin adduct of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in humans. Carcinogenesis, 39, 1455–1462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sabbioni, G., & Turesky, R. J. (2017). Biomonitoring human albumin adducts: The past, the present, and the future. Chemical Research in Toxicology, 30, 332–366.

    Article  CAS  PubMed  Google Scholar 

  17. Wang, Y., Villalta, P. W., Peng, L., et al. (2017). Mass spectrometric characterization of an acid labile adduct formed with 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine and albumin in humans. Chemical Research in Toxicology, 30, 705–714.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Murray, S., Gooderham, N. J., Boobis, A. R., et al. (1989). Detection and measurement of MeIQx in human urine after ingestion of a cooked meat meal. Carcinogenesis, 10, 763–765.

    Article  CAS  PubMed  Google Scholar 

  19. Stillwell, W. G., Turesky, R. J., Sinha, R., & Tannenbaum, S. R. (1999). N-oxidative metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in humans: Excretion of the N2-glucuronide conjugate of 2-hydroxyamino-MeIQx in urine. Cancer Research, 59, 5154–5159.

    CAS  PubMed  Google Scholar 

  20. Zhang, L., **a, Y., **a, B., et al. (2016). High throughput and sensitive analysis of urinary heterocyclic aromatic amines using isotope-dilution liquid chromatography-tandem mass spectrometry and robotic sample preparation system. Analytical and Bioanalytical Chemistry, 408, 8149–8161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gu, D., Raymundo, M. M., Kadlubar, F. F., & Turesky, R. J. (2011). Ultraperformance liquid chromatography-tandem mass spectrometry method for biomonitoring cooked meat carcinogens and their metabolites in human urine. Analytical Chemistry, 83, 1093–1101.

    Article  CAS  PubMed  Google Scholar 

  22. Guo, J., Yonemori, K., Marchand, L. L., & Turesky, R. J. (2015). A method to biomonitor the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in dyed hair by ultra-performance liquid chromatography-Orbitrap high resolution multistage mass spectrometry. Analytical Chemistry, 87, 5872–5877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Goodenough, A. K., Schut, H. A., & Turesky, R. J. (2007). Novel LC-ESI/MS/MSn method for the characterization and quantification of 2′-deoxyguanosine adducts of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by 2-D linear quadrupole ion trap mass spectrometry. Chemical Research in Toxicology, 20, 263–276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bessette, E. E., Spivack, S., Goodenough, A. K., et al. (2010). Identification of carcinogen DNA adducts in human saliva by linear quadrupole ion trap/multistage tandem mass spectrometry. Chemical Research in Toxicology, 23, 1234–1244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Konorev, D., Koopmeiners, J. S., Tang, Y., et al. (2015). Measurement of the heterocyclic amines 2-amino-9h-pyrido[2,3-b]indole and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in urine: Effects of cigarette smoking. Chemical Research in Toxicology, 28, 2390–2399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang, Y., Peng, L., Bellamri, M., et al. (2015). Mass spectrometric characterization of human serum albumin adducts formed with N-oxidized metabolites of 2-amino-1-methylphenylimidazo[4,5-b]pyridine in human plasma and hepatocytes. Chemical Research in Toxicology, 28, 1045–1059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Turesky, R. J., Liu, L., Gu, D., et al. (2013). Biomonitoring the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in hair: Impact of exposure, hair pigmentation, and cytochrome P450 1A2 phenotype. Cancer Epidemiology, Biomarkers & Prevention, 22, 356–364.

    Article  CAS  Google Scholar 

  28. Kulp, K. S., Knize, M. G., Malfatti, M. A., et al. (2000). Identification of urine metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine following consumption of a single cooked chicken meal in humans. Carcinogenesis, 21, 2065–2072.

    Article  CAS  PubMed  Google Scholar 

  29. Frandsen, H. (2008). Biomonitoring of urinary metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) following human consumption of cooked chicken. Food and Chemical Toxicology, 46, 3200–3205.

    Article  CAS  PubMed  Google Scholar 

  30. Shah, F. U., Barri, T., Jönsson, J. Å., & Skog, K. (2008). Determination of heterocyclic aromatic amines in human urine by hollow-fibre supported liquid membrane extraction and liquid chromatography-ultraviolet detection system. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 870, 203–208.

    Article  CAS  PubMed  Google Scholar 

  31. Busquets, R., Frandsen, H., Jönsson, J. Å., et al. (2013). Biomonitoring of dietary heterocyclic amines and metabolites in urine by liquid phase microextraction: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a possible biomarker of exposure to dietary PhIP. Chemical Research in Toxicology, 26, 233–240.

    Article  CAS  PubMed  Google Scholar 

  32. Dingley, K. H., Curtis, K. D., Nowell, S., et al. (1999). DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine. Cancer Epidemiology, Biomarkers & Prevention, 8, 507–512.

    CAS  Google Scholar 

  33. Magagnotti, C., Orsi, F., Bagnati, R., et al. (2000). Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (PhIP) in humans. International Journal of Cancer, 88, 1–6.

    Article  CAS  PubMed  Google Scholar 

  34. Cooper, K. M., Jankhaikhot, N., & Cuskelly, G. (2014). Optimised extraction of heterocyclic aromatic amines from blood using hollow fibre membrane liquid-phase microextraction and triple quadrupole mass spectrometry. Journal of Chromatography. A, 1358, 20–28.

    Article  CAS  PubMed  Google Scholar 

  35. Alexander, J., Reistad, R., Hegstad, S., et al. (2002). Biomarkers of exposure to heterocyclic amines: Approaches to improve the exposure assessment. Food and Chemical Toxicology, 40, 1131–1137.

    Article  CAS  PubMed  Google Scholar 

  36. Bessette, E. E., Yasa, I., Dunbar, D., et al. (2009). Biomonitoring of carcinogenic heterocyclic aromatic amines in hair: A validation study. Chemical Research in Toxicology, 22, 1454–1463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hegstad, S., Lundanes, E., Reistad, R., et al. (2000). Determination of the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human hair by solid phase extraction and gas chromatography-mass spectrometry. Chromatographia, 52, 499–504.

    Article  CAS  Google Scholar 

  38. Marchand, L., Yonemori, K., White, K. K., et al. (2016). Dose validation of PhIP hair level as a biomarker of heterocyclic aromatic amines exposure: A feeding study. Carcinogenesis, 37, 685–691.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cai, T., Yao, L., & Turesky, R. J. (2016). Bioactivation of heterocyclic aromatic amines by UDP glucuronosyltransferases. Chemical Research in Toxicology, 29, 879–891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Preston, G. W., & Phillips, D. H. (2019). Protein adductomics: Analytical developments and applications in human biomonitoring (Review). Toxics, 7, 29.

    Article  CAS  PubMed Central  Google Scholar 

  41. Kataoka, H., Inoue, T., Ikekita, N., & Saito, K. (2014). Development of exposure assessment method based on the analysis of urinary heterocyclic amines as biomarkers by on-line in-tube solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry, 406, 2171–2178.

    Article  CAS  PubMed  Google Scholar 

  42. Matoso, V., Bargi-Souza, P., Ivanski, F., et al. (2019). Acrylamide: A review about its toxic effects in the light of Developmental Origin of Health and Disease (DOHaD) concept. Food Chemistry, 283, 422–430.

    Article  CAS  PubMed  Google Scholar 

  43. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. (1994). Some industrial chemicals. IARC Monographs, 60, Supl. 7, Lyon.

    Google Scholar 

  44. Mojska, H., Gielecińska, I., Zielińska, A., et al. (2015). Estimation of exposure to dietary acrylamide based on mercapturic acids level in urine of Polish women post-partum and an assessment of health risk. Journal of Exposure Science & Environmental Epidemiology, 26, 1–8.

    Google Scholar 

  45. Rifai, L., & Saleh, F. A. (2020). A review on acrylamide in food: Occurrence, toxicity, and mitigation strategies. International Journal of Toxicology, 39, 93–102.

    Article  CAS  PubMed  Google Scholar 

  46. Huang, M., Jiao, J., Wang, J., et al. (2018). Associations of hemoglobin biomarker levels of acrylamide and all-cause and cardiovascular disease mortality among U.S. adults: National Health and Nutrition Examination Survey 2003–2006. Environmental Pollution, 238, 852–858.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang, Y., Wang, Q., Cheng, J., et al. (2015). Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry. Analytica Chimica Acta, 894, 54–64.

    Article  CAS  PubMed  Google Scholar 

  48. Wang, Q., Chen, X., Ren, Y., et al. (2017). Toxicokinetics and internal exposure of acrylamide: New insight into comprehensively profiling mercapturic acid metabolites as short-term biomarkers in rats and Chinese adolescents. Archives of Toxicology, 91, 2107–2118.

    Article  CAS  PubMed  Google Scholar 

  49. Guo, J., Yu, D., Lv, N., et al. (2017). Relationships between acrylamide and glycidamide hemoglobin adduct levels and allergy-related outcomes in general US population, NHANES 2005–2006. Environmental Pollution, 225, 506–513.

    Article  CAS  PubMed  Google Scholar 

  50. Kim, T. H., Shin, S., Kim, K. B., et al. (2015). Determination of acrylamide and glycidamide in various biological matrices by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study. Talanta, 131, 46–54.

    Article  CAS  PubMed  Google Scholar 

  51. Zhang, Y., Wang, Q., Zhang, G., et al. (2018). Biomarker analysis of hemoglobin adducts of acrylamide and glycidamide enantiomers for mid-term internal exposure assessment by isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry. Talanta, 178, 825–833.

    Article  CAS  PubMed  Google Scholar 

  52. Yang, M., Frame, T., Tse, C., & Vesper, H. W. (2018). High-throughput, simultaneous quantitation of hemoglobin adducts of acrylamide, glycidamide, and ethylene oxide using UHPLC-MS/MS. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1086, 197–205.

    Article  CAS  PubMed  Google Scholar 

  53. Schettgen, T., Müller, J., Fromme, H., & Angerer, J. (2010). Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 878, 2467–2473.

    Article  CAS  PubMed  Google Scholar 

  54. Frigerio, G., Mercadante, R., Polledri, E., et al. (2019). An LC-MS/MS method to profile urinary mercapturic acids, metabolites of electrophilic intermediates of occupational and environmental toxicants. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 117, 66–76.

    Article  Google Scholar 

  55. Wang, P., Ji, R., Ji, J., & Chen, F. (2019). Changes of metabolites of acrylamide and glycidamide in acrylamide-exposed rats pretreated with blueberry anthocyanins extract. Food Chemistry, 274, 611–619.

    Article  CAS  PubMed  Google Scholar 

  56. Goempel, K., Tedsen, L., Ruenz, M., et al. (2017). Biomarker monitoring of controlled dietary acrylamide exposure indicates consistent human endogenous background. Archives of Toxicology, 91, 3551–3560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

    Beata Janoszka & Magdalena Szumska

Authors
  1. Beata Janoszka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magdalena Szumska
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beata Janoszka .

Editor information

Editors and Affiliations

  1. Environmental Chemistry and Bioanalytics, Nicolaus Copernicus University, Torun, Poland

    Bogusław Buszewski

  2. Faculty of Chemistry, Silesian University of Technology, Gliwice, Poland

    Irena Baranowska

Section Editor information

  1. Centre National de la Recherche Scientifique (CNRS), Institute of Analytical Sciences and Physico-Chemistry for Environment (IPREM, UMR 5254 CNRS-UPPA), Pau, France

    Joanna Szpunar

  2. Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland

    Ryszard Łobiński

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Janoszka, B., Szumska, M. (2022). Determination of Metabolites of Selected Thermally Treated Food-Derived Mutagens and Carcinogens in Biological Material. In: Buszewski, B., Baranowska, I. (eds) Handbook of Bioanalytics. Springer, Cham. https://doi.org/10.1007/978-3-030-63957-0_19-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-63957-0_19-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-63957-0

  • Online ISBN: 978-3-030-63957-0

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation