title: Interspecies homology of cytochrome P-450: toxicological significance of cytochrome P-450 cross-reactive with anti-rat P-448-H antibodies in liver microsomes from dogs, monkeys and humans.
abstract: The mutagenic activation of various promutagens by liver microsomes from dogs, monkeys and humans was investigated. Dog liver microsomes efficiently catalyzed the mutagenic activation of Trp-P-2 and Glu-P-1 followed by IQ and AAF. Monkey liver microsomes were most active in the activation of IQ followed by Glu-P-1, AAF and Trp-P-2. Although there were remarkable individual differences, human liver microsomes were found to be most active in the mutagenic activation of IQ followed by Trp-P-2, Glu-P-1 and AAF. Antibodies against rat P-448-H inhibited the mutagenic activation of Glu-P-1, Trp-P-2 and IQ in rat and dog liver microsomes, and Glu-P-1 and Trp-P-2 in monkey liver microsomes. The activation of Glu-P-1 and IQ in human liver microsomes was also strongly inhibited by anti-P-448-H antibodies. The amounts of cytochrome P-450 cross-reactive with anti-P-448-H antibodies in human liver microsomes highly correlated with the capacity to activate Glu-P-1, Trp-P-2 and IQ but not AAF.
authors.affiliation: Department of Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Kitada
authors.forename: H
authors.initials: H
authors.lastname: Ohi
authors.forename: M
authors.initials: M
authors.lastname: Komori
authors.forename: K
authors.initials: K
authors.lastname: Nagashima
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Muroya
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.forename: T
authors.initials: T
authors.lastname: Kamataki
mesh_terms: D015073:2-Acetylaminofluorene / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D002243:Carbolines / Q000493:pharmacokinetics / Q000633:toxicity; D003429:Cross Reactions; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000276:immunology; D003580:Cytochromes / Q000235:genetics* / Q000276:immunology; D004285:Dogs; D005260:Female; D000882:Haplorhini; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000276:immunology; D009153:Mutagens / Q000493:pharmacokinetics*; D011804:Quinolines / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000235:genetics; D013045:Species Specificity
chemical_list: D002243:Carbolines; D003580:Cytochromes; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2