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. 1986 Aug;67:59–74. doi: 10.1289/ehp.866759

Mutagen formation in a model beef supernatant fraction. IV. Properties of the system.

R T Taylor, E Fultz, M Knize
PMCID: PMC1474427  PMID: 3757961

Abstract

To identify the precursors and elucidate the reaction conditions that yield heterocyclic amine mutagens in cooked meat products and fish, we have used a supernatant 2 (S2) fraction prepared from H2O-homogenized lean round steak. Compounds (MW less than 500) in S2 are the sources of the microsomal-dependent, Salmonella TA 1538 mutagenic activity in open boiled (aqueous), 200 degrees C pressure-heated (aqueous), or 200 to 300 degrees C oven-baked (freeze-dried) homogenates. Combined incorporation-HPLC experiments show that they are also the precursors for frameshift mutagen formation in the outer surfaces of 200 degrees C griddle-fried ground beef. Maximal stimulations of boiled S2 mutagenic activity are given by 10 mM Trp, 2.5 mM creatine phosphate (CP), and synergistically by 10 mM Trp + 2.5 mM CP + 1.0 mM FeSO4 (a mixture abbreviated as S2*). Boiling S2 for 30 hr at the acidic optimum pH of 4.0----600 TA 1538 revertants (no additions) and 1,400 revertants (+CP), while S2*----24,000 revertants/10(8) bacteria/g of dry beef. By the criteria of HPLC, paper electrophoresis, and resistance of the active HPLC fractions to acid-nitrite inactivation, boiled S2 contains 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and a minor amount of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). Boiling S2 with CP doubles the IQ, halves the Trp-P-2, produced traces of MeIQ, and generates an unknown nitrite-resistant mutagen. Boiled S2* contains these same four mutagens, but both the IQ and Trp-P-2 are increased and large amounts of Trp-P-1 also are generated. The identities of IQ, Trp-P-2, and Trp-P-1 were verified by purification and by light-absorption and mass spectra. Their increments in stimulated S2 indicate that Trp (or its degradation products) and CP (or its degradation products) are the beef juice precursors for the indole ring in Trp-P type mutagens and the NH2-imidazole ring in IQ-type mutagens, respectively. Aqueous (pressure) heating or oven-baking S2 for 2 hr at 200 degrees C greatly elevates its TA 1538 activity----45,000 revertants/10(8) bacteria/g of dry beef; dry heating at 300 degrees C----approximately 180,000 revertants/g of dry beef. Along with the increases in total TA 1538 activity at 200 to 300 degrees C, the number of mutagens formed from the less than 500 MW S2 precursors also multiplies.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  2. Bjeldanes L. F., Morris M. M., Felton J. S., Healy S., Stuermer D., Berry P., Timourian H., Hatch F. T. Mutagens from the cooking of food. II. Survey by Ames/Salmonella test of mutagen formation in the major protein-rich foods of the American diet. Food Chem Toxicol. 1982 Aug;20(4):357–363. doi: 10.1016/s0278-6915(82)80099-9. [DOI] [PubMed] [Google Scholar]
  3. Bjeldanes L. F., Morris M. M., Timourian H., Hatch F. T. Effects of meat composition and cooking conditions on mutagen formation in fried ground beef. J Agric Food Chem. 1983 Jan-Feb;31(1):18–21. doi: 10.1021/jf00115a005. [DOI] [PubMed] [Google Scholar]
  4. 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 Sep 8;201(4359):913–916. doi: 10.1126/science.567374. [DOI] [PubMed] [Google Scholar]
  5. Felton J. S., Knize M. G., Wood C., Wuebbles B. J., Healy S. K., Stuermer D. H., Bjeldanes L. F., Kimble B. J., Hatch F. T. Isolation and characterization of new mutagens from fried ground beef. Carcinogenesis. 1984 Jan;5(1):95–102. doi: 10.1093/carcin/5.1.95. [DOI] [PubMed] [Google Scholar]
  6. Hargraves W. A., Pariza M. W. Purification and mass spectral characterization of bacterial mutagens from commercial beef extract. Cancer Res. 1983 Apr;43(4):1467–1472. [PubMed] [Google Scholar]
  7. Hayatsu H., Matsui Y., Ohara Y., Oka T., Hayatsu T. Characterization of mutagenic fractions in beef extract and in cooked ground beef. Use of blue-cotton for efficient extraction. Gan. 1983 Aug;74(4):472–482. [PubMed] [Google Scholar]
  8. Hosaka S., Matsushima T., Hirono I., Sugimura T. Carcinogenic activity of 3-amino-1-methyl-5H-pyrido [4,3-b]indole (Trp-P-2), a pyrolysis product of tryptophan. Cancer Lett. 1981 Jun;13(1):23–28. doi: 10.1016/0304-3835(81)90082-3. [DOI] [PubMed] [Google Scholar]
  9. Jägerstad M., Olsson K., Grivas S., Negishi C., Wakabayashi K., Tsuda M., Sato S., Sugimura T. Formation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in a model system by heating creatinine, glycine and glucose. Mutat Res. 1984 May;126(3):239–244. doi: 10.1016/0027-5107(84)90002-2. [DOI] [PubMed] [Google Scholar]
  10. Lin J. Y., Lee H., Huang H. I. Formation of mutagens in boiled pork extract. Food Chem Toxicol. 1982 Oct;20(5):531–533. doi: 10.1016/s0278-6915(82)80060-4. [DOI] [PubMed] [Google Scholar]
  11. Matsukura N., Kawachi T., Morino K., Ohgaki H., Sugimura T., Takayama S. Carcinogenicity in mice of mutagenic compounds from a tryptophan pyrolyzate. Science. 1981 Jul 17;213(4505):346–347. doi: 10.1126/science.7244619. [DOI] [PubMed] [Google Scholar]
  12. Negishi C., Wakabayashi K., Tsuda M., Sato S., Sugimura T., Saitô H., Maeda M., Jägerstad M. Formation of 2-amino-3,7,8-trimethylimidazo [4,5-f]quinoxaline, a new mutagen, by heating a mixture of creatinine, glucose and glycine. Mutat Res. 1984 Jun-Jul;140(2-3):55–59. doi: 10.1016/0165-7992(84)90042-3. [DOI] [PubMed] [Google Scholar]
  13. Ohgaki H., Kusama K., Matsukura N., Morino K., Hasegawa H., Sato S., Takayama S., Sugimura T. Carcinogenicity in mice of a mutagenic compound, 2-amino-3-methylimidazo[4,5-f]quinoline, from broiled sardine, cooked beef and beef extract. Carcinogenesis. 1984 Jul;5(7):921–924. doi: 10.1093/carcin/5.7.921. [DOI] [PubMed] [Google Scholar]
  14. Ohgaki H., Matsukura N., Morino K., Kawachi T., Sugimura T., Takayama S. Carcinogenicity in mice of mutagenic compounds from glutamic acid and soybean globulin pyrolysates. Carcinogenesis. 1984 Jun;5(6):815–819. doi: 10.1093/carcin/5.6.815. [DOI] [PubMed] [Google Scholar]
  15. Overvik E., Nilsson L., Fredholm L., Levin O., Nord C. E., Gustafsson J. A. High mutagenic activity formed in pan-broiled pork. Mutat Res. 1984 Mar;135(3):149–157. doi: 10.1016/0165-1218(84)90115-0. [DOI] [PubMed] [Google Scholar]
  16. Pariza M. W., Ashoor S. H., Chu F. S., Lund D. B. Effects of temperature and time on mutagen formation in pan-fried hamburger. Cancer Lett. 1979 Jul;7(2-3):63–69. doi: 10.1016/s0304-3835(79)80097-x. [DOI] [PubMed] [Google Scholar]
  17. Plumlee C., Bjeldanes L. F., Hatch F. T. Priorities assessment for studies of mutagen production in cooked foods. J Am Diet Assoc. 1981 Oct;79(4):446–449. [PubMed] [Google Scholar]
  18. Shibamoto T. Heterocyclic compounds found in cooked meats. J Agric Food Chem. 1980 Mar-Apr;28(2):237–243. doi: 10.1021/jf60228a031. [DOI] [PubMed] [Google Scholar]
  19. Shinohara K., Jahan N., Tanaka M., Yamamoto K., Wu R. T., Murakami H., Omura H. Formation of mutagens by amino-carbonyl reactions. Mutat Res. 1983 Dec;122(3-4):279–286. doi: 10.1016/0165-7992(83)90007-6. [DOI] [PubMed] [Google Scholar]
  20. Spingarn N. E., Garvie-Gould C., Vuolo L. L., Weisburger J. H. Formation of mutagens in cooked foods. IV. Effect of fat content in fried beef patties. Cancer Lett. 1981 Mar;12(1-2):93–97. doi: 10.1016/0304-3835(81)90043-4. [DOI] [PubMed] [Google Scholar]
  21. Spingarn N. E., Weisburger J. H. Formation of mutagens in cooked foods. I. Beef. Cancer Lett. 1979 Sep;7(5):259–264. doi: 10.1016/s0304-3835(79)80052-x. [DOI] [PubMed] [Google Scholar]
  22. Sugimura T. Mutagens in cooked food. Basic Life Sci. 1982;21:243–269. doi: 10.1007/978-1-4684-4352-3_21. [DOI] [PubMed] [Google Scholar]
  23. Sugimura T., Sato S. Mutagens-carcinogens in foods. Cancer Res. 1983 May;43(5 Suppl):2415s–2421s. [PubMed] [Google Scholar]
  24. Takayama S., Masuda M., Mogami M., Ohgaki H., Sato S., Sugimura T. Induction of cancers in the intestine, liver and various other organs of rats by feeding mutagens from glutamic acid pyrolysate. Gan. 1984 Mar;75(3):207–213. [PubMed] [Google Scholar]
  25. Takayama S., Nakatsuru Y., Masuda M., Ohgaki H., Sato S., Sugimura T. Demonstration of carcinogenicity in F344 rats of 2-amino-3-methyl-imidazo[4,5-f]quinoline from broiled sardine, fried beef and beef extract. Gan. 1984 Jun;75(6):467–470. [PubMed] [Google Scholar]
  26. Tsuda M., Takahashi Y., Nagao M., Hirayama T., Sugimura T. Inactivation of mutagens from pyrolysates of tryptophan and glutamic acid by nitrite in acidic solution. Mutat Res. 1980 Aug;78(4):331–339. doi: 10.1016/0165-1218(80)90038-5. [DOI] [PubMed] [Google Scholar]
  27. Turesky R. J., Wishnok J. S., Tannenbaum S. R., Pfund R. A., Buchi G. H. Qualitative and quantitative characterization of mutagens in commercial beef extract. Carcinogenesis. 1983;4(7):863–866. doi: 10.1093/carcin/4.7.863. [DOI] [PubMed] [Google Scholar]
  28. Yoshida D., Matsumoto T. Changes in mutagenicity of protein pyrolyzates by reaction with nitrite. Mutat Res. 1978 Sep;58(1):35–40. doi: 10.1016/0165-1218(78)90093-9. [DOI] [PubMed] [Google Scholar]

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