Abstract
In all recent surveys of the aetiology of human cancer, environment has been identified as a major factor (Wynder and Gori, 1977; Higginson and Muir, 1979; Doll and Peto, 1981). In most studies, diet has proven to be the single most important determinant, associated with more cancer deaths than even cigarette smoking. Indeed, in some studies as many as 35% of all cancer deaths have been attributed to dietary factors which exclude alcohol and food additives (Doll and Peto, 1981). There are numerous mechanisms whereby diet might influence the incidence of cancer. However, the identification of mutagenic chemicals in food formed during its processing and/or cooking (Sugimura et al., 1977) has focussed considerable attention on the possible role of these compounds in human cancer. Recently, a number of extremely potent mutagens arising from the Maillard reaction, involving sugars, amino acids and creatine, have been isolated from cooked meat. These are all heterocyclic aromatic amines amongst which the most potent and abundant are 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) (Felton et al., 1986).
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References
Åström, A. and DePierre, J.W. (1985) Metabolism of 2-acetylaminofluorene by eight different forms of cytochrome P-450 isolated from rat liver. Carcinogenesis, 6, 113–20.
Boobis, A.R., Davies, D.S., McQuade, J. and Sesardic, D. (1985) Specificity of isozymes of cytochrome P-450 determined by inhibitory monoclonal antibodies, Br. J. Pharmacol, 86, 511P.
Butler, M.A., Iwasaki, M., Guengerich, F.P. and Kadlubar, F.F. (1989) Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc. Natl. Acad. Sci. USA, 86, 7696–700.
Campbell, M.E., Grant, D.M., Inaba, T. and Kalow, W. (1987) Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes. Drug Metab. Dispos., 15, 237–49.
Doll, R. and Peto, R. (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst., 66, 1191–308.
Edwards, R.J., Murray, B.P., Boobis, A.R. and Davies, D.S. (1989) Identification and location of alpha-helices in mammalian cytochromes P-450. Biochemistry, 28, 3762–70.
Edwards, R.J., Singleton, A.M., Murray, B.P. et al. (1990) An anti-peptide antibody targeted to a specific region of rat cytochrome P-450IA2 inhibits enzyme activity.Biochem., 266, 497–504.
Edwards, R.J., Singleton, A.M., Sesardic, D. et al. (1988) Antibodies to a synthetic peptide that react specifically with a common surface region on two hydrocarboninducible isoenzymes of cytochrome P-450 in the rat. Biochem. Pharmacol., 37, 3735–41.
Felton, J.S., Knize, M.G., Shen, N.H. et al. (1986) Identification of the mutagens in cooked beef. Environ. Health Perspect., 67, 17–24.
Goldstein, J.A. and Linko, P. (1984) Differential induction of two 2,3,7,8-terachlorodibenzo-p-dioxin inducible forms of cytochrome P-450 in extrahepatic versus hepatic tissues. Mol. Pharmacol., 25, 185–91
Gonzalez, F.J., Skoda, R., Kimura, S. et al. (1988) Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature,331, 442–6.
Gooderham, N.J., Rice, J.C., Boobis, A.R. and Davies, D.S. (1988) Differences between hepatic and extrahepatic tissues in the activation of MelQx to a mutagen in the Ames/Salmonella test, Human Toxicol., 7, 79.
Higginson, J. and Muir, C.S. (1979) Environmental carcinogens: misconceptions and limitations of cancer control. J. Natl Cancer Inst., 63, 1291–8.
Murray, B.P., Boobis, A.R., De La Torre, R. et al. (1988) Inhibition of dietary mutagen activation by methylxanthines. Biochem. Soc. Trans., 16, 620–1.
Nebert, D.W., Nelson, D.R., Adesnik, M. et al. (1989) The P-450 superfamily: updated listing of all genes and recommended nomenclature for the chromosomal loci. DNA,8, 1–13.
Pasanen, M., Stenbäck, F., Taskinen, T. et al. (1989) Human placental 7-ethoxy-resorufin O-deethylase activity: inhibition studies and immunological and molecular biological detection of P-450IA1, in Cytochrome P-450: Biochemistry and Biophysics(ed. I. Schuster), Taylor and Francis, London, pp. 532–5.
Parkinson, A., Ryan, D.E., Thomas, P.E. et al. (1986) Chemical modification and inactivation of rat liver microsomal cytochrome P-450c by 2-bromo-4′-nitro-acetophenone. J. Biol. Chem., 261, 11478–86.
Sesardic, D., Boobis, A.R., Edwards, R.J. and Davies, D.S. (1988) A form of cytochrome P-450 in man, orthologous to form d in the rat, catalyses the O-deethylation of phenacetin and is inducible by cigarette smoking. Br. J. Clin. Pharmacol., 26, 363–72.
Sesardic, D., Boobis, A.R., Murray, B.P. et al. (1990a) Furafylline is a potent and selective inhibitor of cytochrome P-450IA2 in man,Br. J. Clin. Pharmacol., 29, 651–63.
Sesardic, D., Edwards, R.J., Davies, D.S. et al. (1990b) High affinity phenacetin O-deethylase is catalysed specifically by cytochrome P-450d (P-450IA2) in the liver of the rat. Biochem. Pharmacol., 39, 489–98.
Sesardic, D., Rich, K.J., Edwards, R.J. et al. (1989) Selective destruction of cytochrome P-450d and associate monooxygenase activity by carbon tetrachloride in the rat. Xenobiotica, 19, 795–811.
Sugimura, T. (1988) New environmental carcinogens in daily life.Trends in Pharmacol. Sci., Elsevier, Cambridge, 9, 205–9.
Sugimura, T., Kawachi, T., Nagao, M. et al. (1977) Mutagenic principle(s) in tryptophan and phenylalanine pyrolysis products. Proc. Japan Acad., 53, 58–61.
Tarrus, E., Cami, J., Roberts, D.J. et al. (1987) Accumulation of caffeine in healthy volunteers treated with furafylline. Br. J. Clin. Pharmacol., 23, 9–18.
Thomas, P.E., Reik, L.M., Ryan, D.E. and Levin, W. (1984) Characterization of nine monoclonal antibodies against rat hepatic cytochrome P-450c. Delineation of at least five spatially distinct epitopes. J. Biol. Chem., 259, 3890–9.
Wynder, E.L. and Gori, G.B. (1977) Contribution of the environment to cancer incidence: an epidemiological exercise. J. Natl. Cancer Inst., 58, 825–32.
Yamazoe, Y., Abu-Zeid, M., Manabe, S. et al. (1988) Metabolic activation of a protein pyrolysate promutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by rat liver microsomes and purified cytochrome P-450. Carcinogenesis, 9,105–9.
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Boobis, A.R., Sesardic, D., Murray, B.P., Edwards, R.J., Davies, D.S. (1991). Specificity and inducibility of cytochrome P-450 catalysing the activation of food-derived mutagenic heterocyclic amines. In: Hlavica, P., Damani, L.A. (eds) N-Oxidation of Drugs. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3112-4_20
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DOI: https://doi.org/10.1007/978-94-011-3112-4_20
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