Induction of the rat hepatic microsomal mixed-function oxidases by two aza-arenes. A comparison with their non-heterocyclic analogues.
The ability of the aza-aromatic polycyclic aromatic hydrocarbons 10-azobenz(a)pyrene and benz(a)acridine to induce the rat hepatic microsomal mixed-function oxidases was compared to that of their non-heterocyclic analogues benz(a)pyrene and benz(a)anthracene respectively. All four hydrocarbons markedly increased the O-deethylations of ethoxyresorufin and ethoxycoumarin, the non-heterocyclic analogues being the more potent. A more modest increase was seen in the O-dealkylation of pentoxyresorufin. All four hydrocarbons induced proteins recognised by antibodies to cytochrome P-450IAI but no increase was seen when antibodies to cytochrome P-450IIB1 were employed. The metabolic activation of benz(a)pyrene and Glu-P-1 to mutagenic intermediates in the Ames test was enhanced by all pretreatments. It is concluded that the aza-aromatic polycyclic hydrocarbons, like their non-heterocyclic analogues, selectively induce the cytochrome P-450I family of proteins.
Ayrton
A D
AD
Department of Biochemistry, University of Surrey, Guildford, U.K.
Trinick
J
J
Wood
B P
BP
Smith
J N
JN
Ioannides
C
C
D000166:Acridines / Q000494:pharmacology*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology; D001580:Benzopyrenes / Q000494:pharmacology*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D007163:Immunosorbent Techniques; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009152:Mutagenicity Tests; D051381:Rats
D000166:Acridines; D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D007093:Imidazoles; D007527:Isoenzymes; C023961:10-azabenzo(a)pyrene; D001564:Benzo(a)pyrene; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene; C032894:benz(a)acridine; D006899:Mixed Function Oxygenases