Food Heating and the Formation of Heterocyclic Aromatic Amine and Polycyclic Aromatic Hydrocarbon Mutagens/Carcinogens

  • Mark G. Knize
  • Cynthia P. Salmon
  • Pilar Pais
  • James S. Felton
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 459)


Heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH) are mutagens and animal carcinogens sometimes formed when foods are heated or processed. Determining their role in cancer etiology depends on comparing human exposures and determining any significant dose-related effect. Chemical analysis of foods shows that flame-grilling can form both PAH and HAA, and that frying forms predominantly HAA. With detection limits of about 0.1 ng/g, amounts found in commercially processed or restaurant foods range from 0.1 to 14 ng/g for HAA, and levels of PAH up to 1 ng/g in a liquid smoke flavoring. Laboratory fried samples have greater amounts of PAH, up to 38 ng/g in hamburgers, and high levels of HAA, over 300 ng/g, are measured in grilled chicken breast. Understanding the processing conditions that form PAH and HAA can lead to methods to greatly reduce their occurrence in processed foods.


Polycyclic Aromatic Hydrocarbon Aromatic Amine Mutagenic Activity Cooking Time Heterocyclic Amine 
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2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine


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  1. Ames, B. N.; McCann, J.; Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutat.Res. 1975, 31, 347–364.CrossRefGoogle Scholar
  2. Badger, G. M.; Kimber, R. W. L. The formation of aromatic hydrocarbons at high temperatures, Part VI. The pyrolysis of tetralin. J. Chem. Soc. 1960, 51,266–270.CrossRefGoogle Scholar
  3. Basel, R. M. U.S. patent 1995, 5,439,691.Google Scholar
  4. Chen, B. H.; Wang, C. Y.; Chiu, C. P. Evaluation of analysis of polycyclic aromatic hydrocarbons in meat products by liquid chromatography. J. Agric. Food Chem. 1996, 44, 2244–2251.CrossRefGoogle Scholar
  5. Chu, M. M. L.; Chen, C. W. The evaluation and estimation of potential carcinogenic risks of polynuclear aromatic hydrocarbons (PAH). United States Environmental Protection Agency Research and Development 1985, 1–29.Google Scholar
  6. Commoner, B.; Vithayathil, A. J.; Dolara, P.; Nair, S.; Madyastha, P.; Cuca, G. C. Formation of mutagens in beef and beef extract during cooking. Science 1978, 201, 913–916.CrossRefGoogle Scholar
  7. Dennis, M. J.; Massey, R. C.; McWeeny, D. J.; Knowles, M. E.; Watson, D. Analysis of polycyclic aromatic hydrocarbons in UK total diets. Food Chem. Toxic. 1983, 21, 569–574.CrossRefGoogle Scholar
  8. Dennis, M. J.; Massey, R. C.; McWeeny, D. J.; Larsson, B.; Eriksson, A.; Sahlberg, G. Comparison of a capillary gas chromatographic and a high-performance liquid chromatographic method of analysis for polycyclic aromatic hydrocarbons in food. J. Chromatogr. 1984, 285, 127–133.CrossRefGoogle Scholar
  9. Doll, R. Nature and nurture: possibilities for cancer control. Carcinogenesis 1996, 17, 177–184.CrossRefGoogle Scholar
  10. El-Bayoumy, K.; Chae, Y-H.; Upadhyaya, P.; Rivenson, A.; Kurtzke, C.; Reddy, B.; Hecht, S. S. Comparative tumorigenicity of benzo[a]pyrene, 1-nitropyrene, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administered by gavage to female CD rats. Carcinogenesis 1995, 16, 431–434.CrossRefGoogle Scholar
  11. Felton, J. S.; Fultz, E.; Dolbeare, F. A.; Knize, M. G. Reduction of heterocyclic amine mutagens/carcinogens in fried beef patties by microwave pretreatment. Food Chem. Toxic. 1994, 32, 897–903.CrossRefGoogle Scholar
  12. García Falcón, M. S.; González Amigo, S.; Lage Yusty, M. A.; López de Alda-Villaizán, M. J.; Simal Lozano, J. Enrichment of benzo[a]pyrene in smoked food products and determination by high-performance liquid chromatography-fluorescence detection. J. Chromatogr. A 1996, 753, 207–215.CrossRefGoogle Scholar
  13. Gold, L. S.; Manley, N. B.; Slone, T. H.; Garfinked, B. G.; Rohlbach, L.; Ames, B. N. The fifth plot of the carcinogenic potency database: results in animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989. Environ. Health Perpec. 1993, 100, 65–135.CrossRefGoogle Scholar
  14. Gross, G. A. Simple methods for quantifying mutagenic heterocyclic amines in food products. Carcinogenesis 1990, 11, 1597–1603.CrossRefGoogle Scholar
  15. Gross, G. A.; Grüter, A. Quantitation of mutagen i c/carcinogenic heterocyclic aromatic amines in food products. J. Chromatogr. 1992, 592, 271–278.CrossRefGoogle Scholar
  16. Gross, G. A.; Turesky, R. J.; Fay, L. B.; Stillwell, W. G.; Skipper, P. L.; Tannenbaum, S. R. Heterocyclic amine formation in grilled bacon, beef, and fish, and in grill scrapings. Carcinogenesis 1993, 14, 2313–2318.CrossRefGoogle Scholar
  17. Hatch, F. T.; Knize, M. G.; Moore, D. H.; Felton, J. S. Quantitative correlation of mutagenic and carcinogenic potencies for heterocyclic amine from cooked foods and additional aromatic amines. Mutat. Res. 1992, 271, 269–287.CrossRefGoogle Scholar
  18. Howard, J. W.; Fazio, T. Review of polycyclic aromatic hydrocarbons in foods: analytical methodology and reported findings of polycyclic aromatic hydrocarbons in foods. J. Assoc. Off. Anal. Chem. 1980, 63, 1077–1104.Google Scholar
  19. Johansson, M. A. E.; Knize, M. G.; Jägerstad, M.; Felton, J. S. Characterization of mutagenic activity in instant hot beverage powders. Environ. Molec. Mutag. 1995, 25, 154–161.CrossRefGoogle Scholar
  20. Knize M. G.; Andresen, B. D.; Healy, S. K.; Shen, N. H.; Lewis, P. R.; Bjeldanes, L. F.; Hatch, F. T.; Felton, J. S. Effect of temperature, patty thickness and fat content on the production of mutagens in fried ground beef. Food Chem. Toxic. 1985, 23, 1035–1040CrossRefGoogle Scholar
  21. Knize M. G.; Dolbeare F. A.; Carroll K. L.; Moore II, D. H.; Felton J. S. Effect of cooking time and temperature on the heterocyclic amine content of fried-beef patties. Food Chem. Toxic. 1994, 32, 595–603.CrossRefGoogle Scholar
  22. Knize, M. G.; Cunningham, P. L.; Jones, A. L.; Griffin, E. A.; Felton, J. S. Mutagenic activity and heterocyclic amine content in cooked grain food products. Food Chem. Toxic. 1993, 32, 15–21.CrossRefGoogle Scholar
  23. Knize, M. G.; Shen, N. H.; Healy, S. K.; Hatch, F. T.; Felton, J. S. The use of bacterial mutation tests to monitor chemical isolation of the mutagens in cooked beef. Devel, Ind. Microbiol. 1987, 28, 171–180.Google Scholar
  24. Knize, M. G.; Sinha, R.; Rothman, N.; Brown, E. D.; Salmon, C. P.; Levander, O. A.; Cunningham P. L.; Felton J. S. Fast-food meat products have relatively low heterocyclic amine content. Food Chem. Toxic. 1995, 33, 545–551.CrossRefGoogle Scholar
  25. Larsson, B. K.; Shalberg, G. P.; Eriksson, A. T.; Busk, L. Å. Polycyclic aromatic hydrocarbons in grilled food. J. Agric. Food Chem. 1983, 31, 867–873.CrossRefGoogle Scholar
  26. Lawrence, J. F. Determination of nanogram/kilogram of polycyclic aromatic hydrocarbons in foods by HPLC with fluorescence detection. Intern. J. Environ. Anal. Chem. 1986, 24, 113–131.CrossRefGoogle Scholar
  27. Lawrence, J. F.; Weber, D. F. Determination of polycyclic aromatic hydrocarbons in Canadian samples of processed vegetable and dairy products by liquid chromatography with fluorescence detection. J. Agric. Food Chem. 1984, 32, 794–797.CrossRefGoogle Scholar
  28. Lawrence, J. F.; Weber, D. F. Determination of polycyclic aromatic hydrocarbons in some Canadian commercial fish, shellfish, and meat products by liquid chromatography with confirmation by capillary gas chromatography-mass spectrometry. J. Agric. Food Chem. 1984, 32, 789–793.CrossRefGoogle Scholar
  29. Layton, D. W.; Bogen, K. T.; Knize, M. G.; Hatch, F. T.; Johnson, V. M.; Felton, J. S. Cancer risk of heterocyclic amines in cooked foods: An analysis and implications for research. Carcinogenesis. 1995, 16, 39–52.CrossRefGoogle Scholar
  30. Lijinsky, W. The formation and occurrence of food-associated polycyclic aromatic hydrocarbons associated withfood. Mutat. Res. 1991, 259, 251–261.CrossRefGoogle Scholar
  31. Lijinsky, W.; Raha, C. R. The pyrolysis of 2-methyl-naphthalene. J. Org. Chem. 1961, 26, 3566–3567.CrossRefGoogle Scholar
  32. Makamura, T.; Ysuji, K. Japanese patent 1986, 61–25345.Google Scholar
  33. Manabe, S.; Kurihara, N.; Wada, O.; Izumikawa, S.; Asakuna, K.; Morita, M. Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, in airborne particles and diesel-exhaust particles. Environ. Pollut. 1993, 80, 281–286.CrossRefGoogle Scholar
  34. Manabe, S.; Tohyama, K.; Wada, O.; Aramaki, T. Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5–b]pyridine (PhIP), in cigarette smoke condensate. Carcinogenesis 1991, 12, 1945–1947.CrossRefGoogle Scholar
  35. Nadon, L.; Siemiatycki, J.; Dewar, R.; Krewski, D.; Gerin, M. Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons. Am. J. Ind. Med. 1995, 28, 303–324.CrossRefGoogle Scholar
  36. Nagao, M.; Honda, M.; Seino, Y; Yahagi, T.; Sugimura, T. Mutagenicities of smoke condensates and the charred surface of fish and meat. Cancer Lett. 1977, 2, 221–226.CrossRefGoogle Scholar
  37. Ohgaki, H.; Takayama, S.; Sugumura, T. Carcinogenicities of heterocyclic amines in cooked food. Mutat. Res. 1991, 259, 399–410.CrossRefGoogle Scholar
  38. Övervik, E.; Kleman, M.; Berg, I.; Gustafsson J-Å. Influence of creatine, amino acids and water on the formation of the mutagenic heterocyclic amines found in cooked meat. Carcinogenesis 1989, 10, 2293–2301.CrossRefGoogle Scholar
  39. Rivera, L.; Curto, M. J. C.; Pais, P.; Galceran, M. T.; Puignou, L. Solid-phase extraction for the selective isolation of polycyclic aromatic hydrocarbons, azaarenes, and heterocyclic amines in charcoal-grilled meat. J. Chromatogr. A 1996, 719, 85–94.Google Scholar
  40. Robbana-Barnat, S.; Rabache, M.; Rialland E.; Fradin, J. Heterocyclic amines: Occurrence and prevention in cooked food. Environ. Health Persp. 1996, 104, 280–288.CrossRefGoogle Scholar
  41. Salmon, C. P.; Knize, M. G.; Felton, J. S. Effects of marinating on heterocyclic amine carcinogen production in grilled chicken (Food Chem. Toxic. 1997, 35, 433–441).CrossRefGoogle Scholar
  42. Sheilds, P. G.; Xu, G. X.; Blot, W. J.; Fraumeni Jr., J. F.; Trivers, G. E.; Pellizzari, E. D.; Qu, Y. H.; Gao, Y. T.; Harris, C. C. Mutagens from heated Chinese and U.S. cooking oils. J. Natl. Cancer Inst. 1995, 87, 836–841.CrossRefGoogle Scholar
  43. Shirai, T.; Sano, M.; Tamano, S.; Takahashi, S.; Hirose, M.; Futakuchi, M.; Hasegawa, R.; Imaida, K; Matsumoto, K-I.; Wakabayashi, K.; Sugimura, T.; Ito, N. The prostate: A target for the carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine derived from cooked foods. Cancer Res. 1997, 57, 195–198.Google Scholar
  44. Sinha, R.; Rothman, N.; Brown, E.; Levander, O.; Salmon, C. P.; Knize, M. G.; Felton, J. S. High concentrations of the carcinogen 2-amino-1-methyl-6-imidazo[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method. Cancer Res. 1995, 55, 4516–4519.Google Scholar
  45. Skog, K. Cooking procedures and food mutagens: A literature review. Food Chem. Toxic. 1993, 31, 655–675.CrossRefGoogle Scholar
  46. Skog, K.; Jägerstad, M.; Laser Reuterswärd, A. Inhibitory effect of carbohydrates on the formation of mutagens in fried beef patties. Food Chem. Toxic. 1992, 30, 681–688.CrossRefGoogle Scholar
  47. Skog, K.; Steineck, G.; Augustsson, K.; Jägerstad, M. Effect of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues. Carcinogenesis 1995, 16, 861–867.CrossRefGoogle Scholar
  48. Stavric, B. Biological significance of trace levels of mutagenic heterocyclic aromatic amines (HAAs) in the human diet: a critical review. Food Chem. Toxic. 1994, 32, 977–994.CrossRefGoogle Scholar
  49. Sugimura, T.; Nagao, M.; Kawachi, T.; Honda, M.; Yahagi, T.; Seino, Y; Sato, S.; Matsukura, N.; Matsushima, T.; Shirai, A.; Sawamura, M.; Matsumoto, H. Mutagen-carcinogens in foods with special reference to highly mutagenic pyrolytic products in broiled foods. In Origins of Human Cancer, Hiatt, H.H.; Watson, J.D.; Winsten, J.A., Eds.; Cold Spring Harbor, New York, 1977, 1561–1577.Google Scholar
  50. Thiebaud, H. P.; Knize, M. G.; Kuzmicky, P. A.; Felton, J. S.; Hsieh, D. P. Mutagenicity and chemical analysis of fumes from cooking meat. J. Agric. Food Chem. 1994, 42, 1502–1510.CrossRefGoogle Scholar
  51. Tikkanen, L. M.; Sauri, T. M.; Latva-Kala, K. J. Screening of heat-processed Finnish foods for the mutagens 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine. Food Chem. Toxic. 1993, 31, 717–721.CrossRefGoogle Scholar
  52. Vaessen, H. A. M. G.; Schuller, P. L.; Jekel, A. A.; Wilbers, A. M. M. A. Polycyclic aromatic hydrocarbons in selected foods; analysis and occurrence. Toxicol Environ. Chem. 1984, 7, 297–324.CrossRefGoogle Scholar
  53. Vainiotalo, S.; Matveinen, K.; Reunamen, A. GC/MS Determination of the mutagenic heterocyclic amines MeIQx and DiMeIQx in cooking fumes. Fresenius J. Anal. Chem. 1993, 345, 462–466.CrossRefGoogle Scholar
  54. Vikse, R.; Joner, P. E. Mutagenicity, creatine, and nutrient contents of pan fried meat from various animal species. Acta Vet. Scand. 1993, 34, 1–7.Google Scholar
  55. Vogelstein, B.; Kinzler, W. W. Carcinogens leave fingerprints. Nature 1992, 355, 209–210.CrossRefGoogle Scholar
  56. Wakabayashi, K.; Kim, I-S.; Kurosaka, R.; Yamaizumi, Z.; Ushiyams, H.; Takahashi, M.; Koyota, A.; Tada, A.; Nukaya. H.; Goto, S.; Sugimura, T.; Nagao, M. In Heterocyclic amines in cooked foods: possible human carcinogens; Adamson, R.H.: Gustafsson, J-A.: Ito, N.: Nagao, M.; Sugimura, T.; Wakabayashi, K.; Yamazoe, Y., Eds.; Princeton Scientific Publishing, Princeton, NJ, USA, 1995, p. 39.Google Scholar
  57. Wakabayashi, K.; Nagao, M.; Esumi, H.; Sugimura T. Food-derived mutagens and carcinogens. Cancer Res. 1992, 52 (suppl.), 2092s-2098s.Google Scholar
  58. Wang, Y. Y.; Vuolo, L. L.; Springarn, N. E.; Weisburger, J. H. Formation of mutagens in cooked foods, V. The mutagen reducing effect of soy protein concentrates and antioxidants during frying of beef. Cancer Lett. 1982, 16, 179–186.CrossRefGoogle Scholar
  59. Wynder, E. L.; Gori, G. B. Contribution of the environment to cancer incidence: an epidemiologic exercise. J. Nat. Cancer Inst. 1977, 58, 825–832.Google Scholar
  60. Yabiky, H. Y.; Martins, M. S.; Takahashi, M. Y Levels of benzo[a]pyrene and other polycyclic aromatic hydrocarbons in liquid smoke flavour and some smoked foods. Food Addit. Contamin. 1993, 10, 399–405.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Mark G. Knize
    • 1
  • Cynthia P. Salmon
    • 1
  • Pilar Pais
    • 1
  • James S. Felton
    • 1
  1. 1.Biology and Biotechnology Research Program Lawrence Livermore National LaboratoryUniversity of CaliforniaLivermoreUSA

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