In vivo induction of cytochrome P450 CYP3A expression in rat leukocytes using various inducers.
Although the induction of cytochromes P450 3A (CYP3A) is relatively well characterized in liver, its inducibility in an easily available tissue such as the peripheral leukocytes is not known. The purpose of this study was, therefore, to determine if CYP3A is inducible in vivo in peripheral leukocytes. Microsomes from rat leukocytes and liver were examined for CYP3A protein expression using Western blotting with a rabbit polyclonal antibody against rat CYP3A. Although CYP3A was not detected in control leukocytes, in vivo treatment with known CYP3A inducers (dexamethasone, clotrimazole, phenobarbital, pregnenolone-16 alpha-carbonitrile) resulted in CYP3A leukocyte levels of 0.2-0.8 pmol/mg protein. This leukocyte induction was approximately 1000-fold lower than in induced liver. Interestingly, there was an apparent linear relationship between leukocyte and liver CYP3A contents (r2 = 0.748, n = 29). These results not only demonstrate for the first time that CYP3A is inducible in rat leukocytes after in vivo treatment with various CYP3A inducers, but also suggest that peripheral leukocytes could be used to assess induction in vivo.
Mahnke
A
A
Pharmacotoxicology and Pharmacogenetics Laboratory (CNRS URA 147), Gustave-Roussy Institute, Villejuif, France.
Roos
P H
PH
Hanstein
W G
WG
Chabot
G G
GG
D000818:Animals; D015153:Blotting, Western; D003022:Clotrimazole / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000097:blood; D010634:Phenobarbital / Q000494:pharmacology; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D011285:Pregnenolone Carbonitrile; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D003022:Clotrimazole; D010634:Phenobarbital