Identification of the hepatic cytochrome P-450 isozymes induced and decreased by picloram.
Microsomes from male rats treated with picloram (100 mg/kg/day) for 7 days showed a 48% decrease in 16 alpha-hydroxylase activity when incubated with (4-14C) androstenedione. These data are consistent with the assertion that picloram decreases the titer of hepatic male specific cytochrome P-450h. Several lines of evidence suggested that picloram is an inducer of hepatic cytochrome P-450 in male rats. First, SDS polyacrylamide gel electrophoresis revealed an intensified hepatic microsomal polypeptide (MW 54,000) following picloram pretreatment. This polypeptide co-migrated with protein bands which were correspondingly intensified after pretreatment with known inducers of cytochrome P-450d (3-methylcholanthrene and isosafrole). Second, no increase in the binding of metyrapone to picloram treated microsomes was noted compared with controls, suggesting no increase in phenobarbital-inducible forms of cytochrome P-450. Third, hepatic microsomes from picloram treated rats activated 2-amino-3-methylimidazo [4,5-f] quinoline (a cytochrome P-450d mediated catalysis) causing a 5-fold increase in the number of induced Salmonella typhimurium TA98 revertant colonies formed compared with control microsomes. Fourth, the binding of n-octylamine to hepatic microsomes from picloram-treated rats showed, like microsomes from 3-methylcholanthrene-treated rats, an increase in the proportion of high-spin cytochrome P-450 present. Cytochrome P-450d is known to be a high spin haemoprotein.
Reidy
G F
GF
National Occupational Health and Safety Commission, University of Sydney, NSW, Australia.
Murray
M
M
Rose
H A
HA
Bonin
A M
AM
Baker
R S
RS
Stacey
N H
NH
D000735:Androstenedione / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000032:analysis; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007527:Isoenzymes / Q000032:analysis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008797:Metyrapone / Q000378:metabolism; D008970:Molecular Weight; D009153:Mutagens / Q000378:metabolism; D010846:Picloram / Q000494:pharmacology*; D010848:Picolinic Acids / Q000494:pharmacology*; D011804:Quinolines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D007527:Isoenzymes; D009153:Mutagens; D010848:Picolinic Acids; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D000735:Androstenedione; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D010846:Picloram; D008797:Metyrapone