Effects of picloram on xenobiotic biotransformation in rat liver.
1. The effect of picloram on model xenobiotic substrate biotransformation in vivo was studied in female and male rat liver. 2. Treatment with picloram had little effect on epoxide hydratase and glutathione S-transferase activity, but caused a dose-dependent increase in ethoxyresorufin-O-deethylase activity and a concomitant decrease in aldrin epoxidase activity in male rats. 3. Treatment of male rats with equivalent doses of 2-acetylaminofluorene, 2-amino-anthracene and picloram induced ethoxyresorufin-O-deethylase activity to the same degree. 4. Treatment of female rats with picloram resulted in dose-dependent increases in ethoxyresorufin and ethoxycoumarin-O-deethylation without decreasing aldrin epoxidase activity. 5. Picloram binds to liver microsomal preparations from rats pretreated with phenobarbitone and/or 3-methylcholanthrene, giving a type I spectrum. 6. The results indicate that picloram is a 3-methylcholanthrene-type inducer, and the implications are discussed.
Occupational Health Division, University of Sydney, New South Wales, Australia.
G F
GF
Reidy
H A
HA
Rose
N H
NH
Stacey
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010088:Oxidoreductases / Q000096:biosynthesis; D010599:Pharmacokinetics; D010846:Picloram / Q000494:pharmacology*; D010848:Picolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D002273:Carcinogens; D010848:Picolinic Acids; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C019647:aldrin epoxidase; D019363:Cytochrome P-450 CYP1A1; D010846:Picloram