Mutagens in Cooked Foods-Metabolism and Genetic Toxicity

  • J. S. Felton
  • L. F. Bjeldanes
  • F. T. Hatch
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 177)

Abstract

Recently developed in our laboratories is an efficient extraction procedure incorporating XAD resin adsorption which yields from 200°C grilled ground beef an extract containing 230 SalmonellaTA1538 revertants per g fresh weight of original ground beef. These mutagenic components are specific for frameshift-sensitive Salmonellastrains and have an absolute requirement for metabolic activation. S9 activation by cytochrome P-448 inducers, Aroclor 1254 (PCB), 3-methylcholanthrene (3-MC) and B-naphthoflavone(BNF1), resulted in the largest mutagenic response. Phenobarbital induction gave 20% of the PCB response and Pregnenolone-16a-carbonitrile and corn oil were inactive. Human liver microsomes and BNF-induced rodent intestinal S9 were also active metabolizing fractions. Normal-phase HPLC separation of methanol-extractable metabolites generated from reaction of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ), a mutagenic component of broiled food, rat liver microsomes and cofactors resulted in one direct-acting mutagenic peak and a second more polar peak still requiring metabolic activation. Two potent thermally-produced bacterial mutagens, Trp-P-2 and IQ, were examined in mammalian cells. In excision repair-deficient CHO cells, Trp-P-2 exposure caused cytotoxicity, mutagenicity (thioguanine and azaadenine resistances), sister chromatid exchange, and chromosomal aberrations at concentrations more than 30-fold lower than those for IQ. In normal repair-proficient CHO cells Trp-P-2 was one-half as active and IQ was inactive. Relative to Trp-P-2, IQ is much more potent in the Salmonellabacterial system than in mammalian CHO cells.

Keywords

Toxicity Adduct Tryptophan Indole Tritium 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference List

  1. Felton, J., Healy, S., Stuermer, D., Berry, C., Timourian, H., Hatch, F.T., Morris, M. & Bjeldanes, L.F. (1981a). Mutagens from the cooking of food. (I). Improved isolation and characterization of mutagenic fractions from cooked ground beef. Mutation Res. 88, 33 - 44.PubMedCrossRefGoogle Scholar
  2. Felton, J.S. Nebert, D.W., and Thorgiersson, S.S. (1976). Genetic differences in 2-acetylaminofluorene mutagenicity in vitro associated with mouse hepatic aryl hyrocarbon hydroxylase activity induced by polycyclic aromatic compounds. Mol. Pharmacol. 12, 225–233.Google Scholar
  3. Felton, J.S., Healy, S.K., Knize, M., Stuermer, D.H., Berry, P.W., Timourian, HJ., Hatch, F.T., Morris, M., and Bjeldanes, L.F. (1981b) In vitro human and rodent metabolism of mutagenic fractions from cooked ground beef. Environmental Mutagenesis 3, 342.Google Scholar
  4. Felton, J.S., Knize, M.G., Wood, C., Wuebbles, B.J., Healy, S.K., Stuermer, D.H., Bjeldanes, L.F., Kimble, B.J., and Hatch, F.T. (1984). Isolation and characterization of new mutagens from fried ground beef. Carcinogenesis, 5, 95–102.PubMedCrossRefGoogle Scholar
  5. Isono, K. and Yourno, J. (1974). Chemical carcinogens as frameshift mutagens: Salmonella DNA sequence sensitive to mutagenesis by polycyclic carcinogens. Proc. Natl. Acad. Sci. USA 71, 1612–1617.PubMedCrossRefGoogle Scholar
  6. Levin, D.E., Hollstein, M., Christman, M.F., Schwiers, E.A., and Ames, B.N. (1982). A new Salmonella tester strain (TA 102) with A-T base pairs at the site of mutation detects oxidative mutagens. Proc. Natl. Acad. Sci. USA 79, 7445–7449.PubMedCrossRefGoogle Scholar
  7. Matsukura, N., Kawachi, T., Morino, K., Ohgaki, H., Sugimura, T., and Takayama, S. (1982). Carcinogenicity in mice of mutagenic compounds from a tryptophan pyrolyzate. Science, 213, 346.CrossRefGoogle Scholar
  8. Moore, D. and Felton, J.S. (1983). A microcomputer program for analyzing Ames test data. Mutation Res. 119, 95–102.PubMedCrossRefGoogle Scholar
  9. Nagao, M., Wakabayashi, K., Kasai, H., Nishimura, S., and Sugimura, T. (1981). Effect of methyl substitution on mutagenicities of 2-amino-3-methylimidazo[4,5-f]quinoline, isolated from broiled sardine. Carcinogenesis, 21147–1149.PubMedCrossRefGoogle Scholar
  10. Rosenkranz, H.S., McCoy, E.D., Sanders, D.R., Butler, M., Kiriazides, D.K., and Mermelstein, R. (1980). Nitropyrenes: Isolation, identification, and reduction of mutagenic impurities in carbon black and toners. Science 209, 1039–1043.PubMedCrossRefGoogle Scholar
  11. Skopek, T.R., Liber, H.L., Kaden, D.A., Thilly, W.G. (1978). Relative sensitivities of forward and reverse mutation assays in Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 75, 4467–4469.Google Scholar
  12. Thompson, L.H., Carrano, A.V., Salazar, E., Felton, J.S., and Hatch, F.T. (1983). Comparative genotoxic effects of the cooked-food-related mutagens Trp-P-2 and IQ in bacteria and cultured mammalian cells, Mutation Res. 117, 243–257.PubMedCrossRefGoogle Scholar
  13. Whong, W.Z., Stewart, J., and Ong, T.M. (1981). Use of the improved arabinose-resistant assay system of Salmonella typhimurium for mutagenesis testing. Environ. Mutagenesis 3, 95–99.CrossRefGoogle Scholar
  14. Yamazoe, Y., Ishii, K., Kamataki, T. and Kato, R. (1981). Structural elucidation of a mutagenic metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole. Drug Metabolism and Disposition 9, 292–296.PubMedGoogle Scholar
  15. Yamazoe, Y., Shimada, M., Kamataki, T., and Kato, R. (1983). Microsomal activation of 2-amino-3-methylimidzao[4,5-5]quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate. Cancer Res. 43, 5768–5774.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • J. S. Felton
    • 1
    • 2
  • L. F. Bjeldanes
    • 1
    • 2
  • F. T. Hatch
    • 1
    • 2
  1. 1.Biomedical Sciences DivisionLawrence Livermore National LaboratoryLivermoreUSA
  2. 2.Department of Nutritional SciencesUniversity of California, BerkeleyLivermoreUSA

Personalised recommendations