The induction of P450 I proteins by aromatic amines may be related to their carcinogenic potential.
The hypothesis has been put forward that genotoxic aromatic amines which induce the P450 I family of haemoproteins, the major enzyme involved in their bioactivation, are more likely to be carcinogenic when compared to those chemicals that fail to do so. Induction of the hepatic P450 I family of proteins by carcinogenic aromatic amines and their non-carcinogenic isomers and analogues was investigated in the rat and correlated to their carcinogenic potential. The activity of the P450 I A1 protein was monitored by the O-deethylation of ethoxyresorufin and of the P450 I A2 by the activation of the premutagen Glu-P-1 to mutagenic intermediates in the Ames test. Results were always confirmed immunologically in Western blots employing antibodies to rat P450 I A1 which recognize both proteins of the P450 I family. With all groups of chemicals used in the present study, the members displaying carcinogenicity were always the more potent inducers, while the non-carcinogenic isomers or analogues displayed little or no induction. It appears that a relationship exists between the carcinogenicity of aromatic amines and their ability to induce hepatic P450 I activity.
Ayrton
A D
AD
Department of Biochemistry, University of Surrey, Guildford, UK.
McFarlane
M
M
Walker
R
R
Neville
S
S
Ioannides
C
C
D000588:Amines / Q000633:toxicity*; D000818:Animals; D001713:Biphenyl Compounds / Q000633:toxicity; D002273:Carcinogens; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003580:Cytochromes / Q000096:biosynthesis*; D004790:Enzyme Induction; D005449:Fluorenes / Q000633:toxicity; D008297:Male; D009281:Naphthalenes / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D001713:Biphenyl Compounds; D002273:Carcinogens; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System; D003580:Cytochromes; D005449:Fluorenes; D009281:Naphthalenes; C010574:biphenyl; C017170:Cyp1a2 protein, rat