Comparative biochemistry of cytochrome P-450 species responsible for the activation of mutagenic food-derived heterocyclic amines

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