When food derived from muscle is heated, potent mutagens are produced. For nearly two decades, LLNL researchers have studied the formation of toxic mutagenic compounds in red meats and other foods containing protein. This report, the first of two installments, focuses on the identification of food mutagens and measurement of their abundance in cooked foods as a function of cooking temperature and time.

F all the toxic substances produced during cooking, the most important are likely to be the heterocyclic amines. For 17 years, LLNL researchers have been identifying these food mutagens, measuring their abundance in cooked foods typical of the Western diet, working to understand how they can trigger malignant tumors in laboratory animals that have been exposed to high mutagen doses, and estimating the importance of human exposures. Our success is largely a function of the interdisciplinary approach we have taken to quantify food mutagens and to study their biological effects. LLNL investigators were the first to identify five of the most important mutagens in heated food, including PhIP and DiMeIQx. We have shown that fried beef may be the most important single source of heterocyclic amines in the human diet and that PhIP accounts for most of the combined mass of mutagens in fried beef cooked well-done. Most nonmeat foods contain low or undetectable levels of these types of compounds, but some cooked protein-containing foods, such as those high in wheat gluten, have significant levels of unknown aromatic amine mutagens. Cooking time and temperature significantly affect the amounts of mutagens generated. For example, reducing the frying temperature of ground beef from 250 to 200 degrees Celsius lowers the mutagenic activity by six- to sevenfold. Microwave pretreatment of meat and discarding the liquid that is formed also greatly reduces the formation of heterocyclic amines. Our related work on dose and risk assessment will be described in a forthcoming article.

Role of Cooked Food in Genetic Changes

The Challenge of Identification

The Cooking Makes a Difference

Key Words: Ames/Salmonella assay; amino-imidazoazaarenes (AIAs); carcinogen; DNA adducts; heterocyclic amines; high-performance liquid chromatography (HPLC); mutagens: airborne,
in cooked foods, in fried beef; mutagenicity; 2-amino-1-methyl-6-phenylimidazo
[4,5-b]pyridine (PhIP); 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ); 2-amino-3,
8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx).


B. N. Ames, J. McCann, and E. Yamasaki, "Method for Detecting Carcinogens and Mutagens with the Salmonella/Mammalian-Microsomal Mutagenicity Test," Mutation Research 31, 347-364 (1975).

T. Sugimura et al., "Mutagen-Carcinogens in Foods with Special Reference to Highly Mutagenic Pyrolytic Products in Broiled Foods," in Origins of Human Cancer, H. H. Hiatt, J. D. Watson, and J. A. Winsten, Eds., (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1977), pp. 1561-1577.

B. Commoner et al., "Formation of Mutagens in Beef and Beef Extract During Cooking," Science 210, 913-916 (1978).

G. A. Gross, "Simple Methods for Quantifying Mutagenic Heterocyclic Aromatic Amines in Food Products," Carcinogenesis 11, 1597 (1990).

For a general review of research on food mutagens, see J. S. Felton and M. G. Knize, "Heterocyclic-Amine Mutagens/Carcinogens in Foods," Handbook of Experimental Pharmacology, Vol. 94/I, C. S. Cooper and P. L. Grover, Eds. (Springer-Verlag, Berlin, Germany, 1990), pp. 471-502.

J. S. Felton et al., "Effect of Microwave Pretreatment on Heterocyclic Aromatic Amine Mutagens/Carcinogens in Fried Beef Patties," Food Chemical Toxicology 32 (10), 897-903 (1994). (UCRL-JC-116450)

For further information contact James S. Felton (510) 422-5656 (felton1@llnl.gov) or
Mark G. Knize (510) 422-8260 (knize1@llnl.gov).

JAMES FELTON joined the Biomedical Sciences Division of Lawrence Livermore National Laboratory as a Senior Biomedical Scientist in 1976. He is currently the Group Leader of the Molecular Toxicology Group of the Biology and Biotechnology Program at the Laboratory. He received his A.B. in Zoology from the University of California, Berkeley, in 1967 and his Ph.D. in Molecular Biology from the State University of New York at Buffalo in 1973. From 1969 until 1976, he was a Fellow of the National Institute of Health, initially in New York and later in Maryland.
In more than 147 professional publications, James Felton has explored the role of diet in carcinogenesis and mutagenesis. He has been a part of the Laboratory's research on food mutagens since it began 17 years ago and has led it for the past 8 years.

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