Abstract
Numerous promutagens have been isolated from the pyrolysates of proteins, amino acids and other constituents of foods. Extensive studies have shown that most of these agents are carcinogenic. The mechanisms involved in the induction of tumours by these compounds have also been examined (Sugimura and Sato, 1983; Matsukura et al., 1981). Trp-P-2 (3-amino-l-methyl-5H-pyrido[4,3-b]indole), Glu-P-1 (2-amino-6-methyl-dipyrido[l,2-a: 3′,2′-d]imidazole) and IQ (2-amino-3-methylimidazo-[4,5-f]quinoline) are heterocyclic amines which are hydroxylated at the N-positions by cytochrome P-450 as a common activation step in mutagenicity (Ishii et al., 1980x, Ishii et al., 1981; Yamazoe et al. , 1983; Kato, 1986). Despite these studies, few data have been reported on species differences in the activation of promutagens, especially with regard to beagle dogs, monkeys and humans. Thus, this review focuses on comparison of the mutagen-producing activities of liver microsomes and purified preparations of cytochrome P-450 from rats, beagle dogs, monkeys and humans using heterocyclic amines as the substrates. The results of molecular cloning and expression in yeast of certain forms of cytochrome P-450 from beagle dogs and monkeys will also be discussed
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Beaune, P.H., Umbenhauer, D.R., Bork, R.W. et al. (1986) Isolation and sequence determination of cDNA clone related to human cytochrome P-450 nifedipine oxidase. Proc. Natl. Acad. Sci. USA, 83, 8064–8.
Haniu, M., Ryan, D.E., Iida, S. et al. (1984) NH2-Terminal sequence analyses of four rat hepatic microsomal cytochrome P-450. Arch. Biochem. Biophys., 235, 304–11.
Ishii, K., Yamazoe, Y., Kamataki, T. and Kato, R. (1980) Metabolic activation of mutagenic tryptophan pyrolysis products by rat liver microsomes. Cancer Res., 40, 2596–600.
Ishii, K., Yamazoe, Y., Kamatkai, T. and Kato, R. (1981) Metabolic activation of glutamic acid pyrolysis products, 2-amino-6-methyldipyrido[1,2-a: 3′,2′-d]-imidazole and 2-aminodipyrido[1,2-a: 3′,2′d]imidozole, by purified cytochrome P-450. Chem. Biol. Interact .38, 1–13.
Jaiswall, K., Nebert, D.W. and Gonzalez, F.T. (1986) Human P3-450: cDNA and complete amino acid sequence. Nucleic Acids Res., 14, 6773–4.
Juchau, M.R., Chao, S.T. and Omiecinski, C.J. (1980) Drug metabolism by the human fetus. Clin. Pharmacokinet .5, 320–59.
Kato, R. (1986) Metabolic activation of mutagenic heterocyclic aromatic amines from protein pyrolysates, CRC Crit. Rev. Toxicol., 16, 307–48.
Kawajiri, K., Gotoh, O., Sogawa, K. et al. (1984) Coding nucleotide sequence of 3-methylcholanthrene-inducible cytochrome P-450d cDNA from rat liver, Proc.Natl. Acad. Sci. USA, 81, 1649–53.
Kimura, S., Gonzalez, F.J. and Nebert, D.W. (1984) The murine Ah locus comparison of the complete cytochrome P1-450 and P3-450 cDNA nucleotide and amino acid sequences. J. Biol. Chem., 259, 10705–13.
Komori, M., Hashizume, T., Ohi, H. et al. (1988) Cytochrome P-450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization. J. Biochem. (Tokyo), 104, 912–16.
Komori, M., Nishio, K., Ohi, H. et al. (1989a) Molecular cloning and sequence analysis of cDNA containing the entire coding region for human fetal liver cytochrome P-450. J. Biochem. (Tokyo), 105, 161–3.
Komori, M., Nishio, K., Fujitani, T. et al. (1989b) Isolation of a new human fetal liver cytochrome P-450 cDNA clone: evidence for expression of a limited number of forms of cytochrome P-450 in human fetal livers. Arch. Biochem. Biophys., 273, 219–25.
Matsukura, N., Kawachi, T., Morio, K. et al. (1981) Carcinogenicity in mice of mutagenic compounds from a tryptphan pyrolysate.Science, 213, 346–7.
Ohta, K., Motoya, M., Komori, M. et al. (1989a) A novel form of cytochrome P-450 in beagle dogs: P-450-D3 is a low spin form of cytochrome P-450 but with catalytic and structural properties similar to PCB P-448-H (P-450d). Biochem. Pharmacol., 38, 91–6.
Ohta, K., Kitada, M., Hashizume, T. et al. (1989c) Purification of cytochrome P-450 from polychlorinated biphenyl-treated crab-eating monkeys: high homology to a form of human cytochrome P-450, Biochim. Biophys. Acta, 996, 142–5.
Okino, S.T., Quattrochi, L.C., Barnes, H.J. et al. (1985) Cloning and characterization of cDNA encoding 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible rabbit mRNAs for cytochrome P-450 isozyme 4 and 6. Proc. Natl. Acad. Sci. USA, 82, 5310–14.
Quattrochi, L.C., Pendurthi, U.R., Okino, S.T. et al. (1986) Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA. Proc. Natl. Acad. Sci. USA, 83, 6731–5.
Shimada, T. and Okuda, Y. (1988) Metabolic activation of environmental carcinogens and mutagens by human liver microsomes. Role of cytochrome P-450 homologous to a 3-methylcholanthrene-inducible isozyme in rat liver. Biochem. Pharmacol.,37, 459–65.
Sugimura, T. and Sato, S. (1983) Mutagens-carcinogens in foods, Cancer Res., 43, 2415–21.
Yabusaki, Y., Shimizu, M., Murakami, H. et al. (1984) Nucleotide sequence of a full-length cDNA coding for 3-methylcholanthrene-induced rat liver P-450MC, Nucleic Acids Res., 12, 2929–38.
Yamazoe, Y., Shimada, M., Maeda, K. et al. (1984) Specificity of four forms of cytochrome P-450 in the metabolic activation of several aromatic amines and benzo(a)pyrene. Xenobiotica, 7, 549–52.
Yamazoe, Y, Shimada, M. Kamataki, T. and Kato, R. (1983) Microsomal activation of 2-amino-3-methyl imidazo[4,5-f]quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate. Cancer Res., 43, 5768–74.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Kamataki, T. et al. (1991). Comparative biochemistry of cytochrome P-450 species responsible for the activation of mutagenic food-derived 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_19
Download citation
DOI: https://doi.org/10.1007/978-94-011-3112-4_19
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-5378-5
Online ISBN: 978-94-011-3112-4
eBook Packages: Springer Book Archive