Abstract

Dietary consumption of heterocyclic aromatic amines (HAA) is considered to be a high-risk factor that substantially contributes to the development of mutagenicity and carcinogenicity in humans. This study provides ample evidence for the plausible association between mutagenicity or carcinogenicity development and dietary intake of heterocyclic amines in humans. The current study intends to assess the degree of heterocyclic amine contaminants in high-temperature cooked meats, their subsequent food intake, and potential health risk estimations.
The meat samples were homogenized, filtered, extracted, and eluted. The list of heterocyclic amines to be identified and quantified included PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine), IQ (2-amino-3-methyl-imidazo[4,5-f] quinolone), and MeIQx (2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline). They were simultaneously isolated and studied using the method of high-pressure liquid chromatography (HPLC). The highest heterocyclic amine concentration was found in chicken (2705.99 ± 6.12 ng/g), beef (574.09 ± 1.52 ng/g), and mutton (342.41 ± 3.69 ng/g). PhIP (73%) was the main heterocyclic amine in chicken. The estimated daily dietary intake or exposure in chicken, mutton, and beef was 0.690, 0.050, and 0.144 ng/kg body weight, respectively. The values for margin of exposure were within the range identified by the European Food Safety Authority for mutton (102.06) and chicken (13.250), but not for beef (3.784).
This significantly high prevalence of heterocyclic amines and the associated health risks are sufficient to warn the public about the high dietary intake of meat and its carcinogenic health hazards. The mutational patterns induced by heterocyclic amines resemble those in human tumors, requiring the use of specific biomarkers like HAA-DNA and HAA-protein adducts. Future prospects are high for integrating these biomarkers into epidemiological studies, which could provide a comprehensive assessment of health risks associated with dietary heterocyclic aromatic amines in human cancer.

Keywords

Cytotoxicity, meat, heterocyclic amines, high pressure liquid chromatography, biomarkers, carcinogenicity, health risk

REFERENCES

1. Shiri P, Roosta A, Ramezanpour S, Amani AM. Editorial: Six-membered heterocycles: their synthesis and bio applications. Frontiers in Chemistry. 2023;11:1229825. https://doi.org/10.3389/fchem.2023.1229825
2. Kabir E, Uzzaman M. A review on biological and medicinal impact of heterocyclic compounds. Results in Chemistry. 2022;4:100606. https://doi.org/10.1016/j.rechem.2022.100606
3. Chen J, Shi X, Zhao R, Tian Z, Zhang L, Yu Q, et al. Effect of pomegranate peel extract on the reduction of heterocyclic amines and quality characteristics of mutton meatballs. Food Quality and Safety. 2023;7:1–9. https://doi.org/10.1093/fqsafe/fyac073
4. Olalekan Adeyeye SA, Ashaolu TJ. Heterocyclic Amine Formation and Mitigation in Processed Meat and Meat Products: A Mini-Review. Journal of Food Protection. 2021;84:1868–1877. https://doi.org/10.4315/JFP-20-471
5. Teng H, Mi Y, Deng H, He Y, Wang S, Ai C, et al. Acylated anthocyanin inhibited the formation of heterocyclic amines in hybrid chemical model system and its underlying mechanism. Food Chemistry: X. 2023;17:100559. https://doi.org/10.1016/j.fochx.2023.100559
6. Hao T, Huang L, Wei Y, Shi M. Copper-Catalyzed Synthesis of Indolyl Benzo[b]carbazoles and Their Photoluminescence Property. Organic Letters. 2021;23(13):5133–5137. https://doi.org/10.1021/acs.orglett.1c01659
7. D’Souza A, D’Souza AS, Mendonca AP, Nayak P, Poddar RK, Sadananda V, et al. Review on green multicomponent synthesis of heterocyclic compounds. International Journal of Health Sciences. 2022;6(S8):4601–4623. https://doi.org/10.53730/ijhs.v6nS8.13250
8. Batool Z, Xia W, Chen J-H, Bi Y, Chen F, Wang M. Quantification of hetero-cyclic amines from different categories of braised beef by optimized UPLC-TQ-XS/ESI method. Food Chemistry. 2023;421:136191. https://doi.org/10.1016/j.foodchem.2023.136191
9. Farvid MS, Sidahmed E, Spence ND, Mante Angua K, Rosner BA, Barnett JB. Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies. European Journal of Epidemiology. 2021;36:937–951. https://doi.org/10.1007/s10654-021-00741-9
10. Niedermaier T, Gredner T, Hoffmeister M, Mons U, Brenner H. Impact of Reducing Intake of Red and Processed Meat on Colorectal Cancer Incidence in Germany 2020 to 2050 – A Simulation Study. Nutrients. 2023;15(4):1020. https://doi.org/10.3390/nu15041020
11. Busquets R, Mitjans D, Puignou L, Galceran MT. Quantification of heterocyclic amines from thermally processed meats selected from a small-scale population-based study. Molecular Nutrition Food Research. 2008;52(12):1408–1420. https://doi.org/10.1002/mnfr.200800048
12. Kobets T, Smith BPC, Williams GM. Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk. Foods. 2022;11(18):2828. https://doi.org/10.3390/foods11182828
13. Fahrer J. Food-Borne Carcinogens. In: Schwab M. editor. Encyclopedia of Cancer. Berlin: Springer; 2016. pp. 1–5. https://doi.org/10.1007/978-3-642-27841-9_7235-1
14. Hwa Yun B, Guo J, Bellamri M, Turesky RJ. DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans. Mass Spectrometry Reviews. 2020;39(1–2):55–82. https://doi.org/10.1002/mas.21570
15. Ahmed T, Ameer HA, Javed S. Pakistan’s backyard poultry farming initiative: impact analysis from a public health perspective. Tropical Animal Health Production. 2021;53:210. https://doi.org/10.1007/s11250-021-02659-6
16. Statista Research Department. Statista Research Department, https://www.statista.com/statistics/756924/pakistan-meat-consumption-per-capita-by-type / (2022, accessed 26 July 2023).
17. Sohaib M, Jamil F. An Insight of Meat Industry in Pakistan with Special Reference to Halal Meat: A Comprehensive Review. Korean Journal for Food Science of Animal Resources. 2017;37(3):329–341. https://doi.org/10.5851/kosfa.2017.37.3.329
18. Aujla KM, Sadiq N. Supply estimate and projection for poultry meat in Pakistan by the year 2030 AD. Pure and Applied Biology. 2018;7(2):460–465. https://doi.org/10.19045/bspab.2018.70057
19. Alsohaimi IH, Khan MR, Ali HM, Azam M. Emergence of mutagenic/carcinogenic heterocyclic amines in traditional Saudi chicken dishes prepared from local restaurants. Food and Chemical Toxicology. 2019;132:110677. https://doi.org/10.1016/j.fct.2019.110677
20. Bellamri M, Walmsley SJ, Turesky RJ. Metabolism and biomarkers of heterocyclic aromatic amines in humans. Genes and Environment. 2021;43:29. https://doi.org/10.1186/s41021-021-00200-7
21. National Cancer Institute. Nutritional Carcinogenesis. Qeios. 2020. https://doi.org/10.32388/DE0377
22. Bukowska B, Duchnowicz P, Tumer TB, Michałowicz J, Krokosz A. Precarcinogens in food – Mechanism of action, formation of DNA adducts and preventive measures. Food Control. 2023;152:109884. https://doi.org/10.1016/j.foodcont.2023.109884
23. Perveen I, Saleem Y, Qazi JI. Determination of Heterocyclic Amines in Ready to Eat Chicken Kabab Commercially Available from Pakistani Markets. Pakistan Journal Zoology. 2020;52(6):2027–2400. https://doi.org/10.17582/journal.pjz/20190509050501
24. Gross GA, Grüter A. Quantitation of mutagegnic/carcinogenic heterocyclic aromatic amines in food products. Journal of Chromatography A. 1992;592(1-2):271–278. https://doi.org/10.1016/0021-9673(92)85095-B
25. Messner C, Murkovic M. Evaluation of a new model system for studying the formation of heterocyclic amines. Journal of Chromatography B. 2004;802(1):19–26. https://doi.org/10.1016/j.jchromb.2003.11.015
26. OECD-FAO Agricultural Outlook 2022-2031. OECD; 2022. https://doi.org/10.1787/f1b0b29c-en
27. Bogdanović T, Pleadin J, Petričević S, Listeš E, Sokolić D, Marković K, et al. The occurrence of polycyclic aromatic hydrocarbons in fish and meat products of Croatia and dietary exposure. Journal of Food Composition and Analysis. 2019;75:49–60. https://doi.org/10.1016/j.jfca.2018.09.017
28. Sahin S, Ulusoy HI, Alemdar S, Erdogan S, Agaoglu S. The Presence of Polycyclic Aromatic Hydrocarbons (PAHs) in Grilled Beef, Chicken and Fish by Considering Dietary Exposure and Risk Assessment. Food Science of Animal Resources. 2020;40(5):675–688. https://doi.org/10.5851/kosfa.2020.e43
29. Carthew P, DiNovi M, Woodrow Setzer R. Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic. Food and Chemical Toxicology. 2010;48:S98–S105. https://doi.org/10.1016/j.fct.2009.10.035
30. Zhang J, Empl MT, Schwab C, Fekry MI, Engels C, Schneider M, et al. Gut Microbial Transformation of the Dietary Imidazoquinoxaline Mutagen MeIQx Reduces Its Cytotoxic and Mutagenic Potency. Toxicological Sciences. 2017;159(1):266–276. https://doi.org/10.1093/toxsci/kfx132
31. Wei M, Wanibuchi H, Nakae D, Tsuda H, Takahashi S, Hirose M, et al. Low-dose carcinogenicity of 2-amino-3-methylimidazo [4,5-f ] quinoline in rats: Evidence for the existence of no-effect levels and a mechanism involving p21Cip / WAF1. Cancer Science. 2011;102(1):88–94. https://doi.org/10.1111/j.1349-7006.2010.01761.x
32. Benjamini Y, Braun H. John W. Tukey’s contributions to multiple comparisons. The Annals of Statistics. 2002;30(6):1576–1594. https://doi.org/10.1214/aos/1043351247
33. Salmon CP, Knize MG, Felton JS, Zhao B, Seow A. Heterocyclic aromatic amines in domestically prepared chicken and fish from Singapore Chinese households. Food and Chemical Toxicology. 2006;44(4):484–492. https://doi.org/10.1016/j.fct.2005.08.022
34. Zaidi R, Rani Rawat P. Identification of Heterocyclic Amines in Indian Home Cooked and Commercially Available Meat Foods. Journal Nutrition and Food Sciences. 2011;1(3):1000107. https://doi.org/10.4172/2155-9600.1000107
35. Lu F, Kuhnle GK, Cheng Q. Vegetable oil as fat replacer inhibits formation of heterocyclic amines and polycyclic aromatic hydrocarbons in reduced fat pork patties. Food Control. 2017;81:113–125. https://doi.org/10.1016/j.foodcont.2017.05.043
36. Erdoğan B, Özdestan‐Ocak Ö. Determination the effects of pumpkin and rosehip seed oils on heterocyclic aromatic amine formation in meatballs by high‐performance liquid chromatography. Journal of Food Processing and Preservation. 2022;46(2):e16299. https://doi.org/10.1111/jfpp.16299
37. Jinap S, Mohd-Mokhtar MS, Farhadian A, Hasnol NDS, Jaafar SN, Hajeb P. Effects of varying degrees of doneness on the formation of Heterocyclic Aromatic Amines in chicken and beef satay. Meat Science. 2013;94(2):202–207. https://doi.org/10.1016/j.meatsci.2013.01.013
38. Jahurul MHA, Jinap S, Ang SJ, Abdul-Hamid A, Hajeb P, Lioe HN, et al. Dietary exposure to heterocyclic amines in high-temperature cooked meat and fish in Malaysia. Food Additives and Contaminants: Part A. 2010;27(8):1060–1071. https://doi.org/10.1080/19440041003801190
39. Omofuma OO, Steck SE, Olshan AF, Troester MA. The association between meat and fish intake by preparation methods and breast cancer in the Carolina Breast Cancer Study (CBCS). Breast Cancer Research and Treatment. 2022;193:187–201. https://doi.org/10.1007/s10549-022-06555-x
40. Zeng M, Wang J, Zhang M, Chen J, He Z, Qin F, et al. Inhibitory effects of Sichuan pepper (Zanthoxylum bungeanum) and sanshoamide extract on heterocyclic amine formation in grilled ground beef patties. Food Chemistry. 2018;239:111–118. https://doi.org/10.1016/j.foodchem.2017.06.097
41. Oz F, Kaya M. The inhibitory effect of black pepper on formation of heterocyclic aromatic amines in high-fat meatball. Food Control. 2011;22(3–4):596–600. https://doi.org/10.1016/j.foodcont.2010.10.010
42. Jain RB. Concentrations of selected heterocyclic aromatic amines among US population aged ≥ 6 years: data from NHANES 2013–2014. Environmental Science and Pollution Research. 2018;25:19859–19874. https://doi.org/10.1007/s11356-018-2210-0
43. Pouzou JG, Costard S, Zagmutt FJ. Probabilistic assessment of dietary exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from consumption of meats and breads in the United States. Food and Chemical Toxicology. 2018;114:361–374. https://doi.org/10.1016/j.fct.2018.02.004
44. Sabally K, Sleno L, Jauffrit J-A, Iskandar MM, Kubow S. Inhibitory effects of apple peel polyphenol extract on the formation of heterocyclic amines in pan fried beef patties. Meat Science. 2016;117:57–62. https://doi.org/10.1016/j.meatsci.2016.02.040
45. Scientific Opinion of the Panel on Contaminants in the Food Chain on a request from the European Commission on Polycyclic Aromatic Hydrocarbons in Food. The EFSA Journal. 2008;724:1–114. https://doi.org/10.2903/j.efsa.2008.724
46. Rozentale I, Zacs D, Bartkiene E, Bartkevics V. Polycyclic aromatic hydrocarbons in traditionally smoked meat products from the Baltic states. Food Additives and Contaminants: Part B. 2018;11(2):138–145. https://doi.org/10.1080/19393210.2018.1440637
47. Duedahl-Olesen L, Aaslyng M, Meinert L, Christensen T, Jensen AH, Binderup M-L. Polycyclic aromatic hydrocarbons (PAH) in Danish barbecued meat. Food Control. 2015;57:169–176. https://doi.org/10.1016/j.foodcont.2015.04.012