Prochloraz as potent inhibitor of benzo[a]pyrene metabolism and mutagenic activity in rat liver fractions.
We have determined how prochloraz, an imidazole antifungal agent, affects the metabolism of benzo[a]-pyrene by hepatic microsomes from 3-methylcholanthrene treated male rats. The prochloraz-like 7,8-benzoflavone was a potent inhibitor of total benzo[a]pyrene metabolism while miconazole was a weak inhibitor. The proportion of benzo[a]pyrene dihydrodiols formed was decreased whereas phenols were increased by the in vitro addition of prochloraz. Furthermore, a good correlation was obtained between the effects of prochloraz on the microsomal formation of benzo[a]pyrene metabolites and on the mutagenic activity of benzo[a]pyrene in the Salmonella typhimurium test.
Antignac
E
E
Laboratoire de Toxicologie Alimentaire, Université de Bordeaux I, Talence, France.
Koch
B
B
Grolier
P
P
Cassand
P
P
Narbonne
J F
JF
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005659:Fungicides, Industrial / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity*; D008825:Miconazole / Q000494:pharmacology; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains
D001571:Benzoflavones; D005659:Fungicides, Industrial; D007093:Imidazoles; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D008825:Miconazole; D003577:Cytochrome P-450 Enzyme System; C045362:prochloraz