Induction of liver cytochrome P450 1A2 expression by flutamide in rats.
OBJECTIVE
To investigate the modulation of liver cytochrome P450 1A2 (CYP1A2) expression by giving flutamide to adult rats.


METHODS
Rats were given 50, 100, and 200 mg/kg po of flutamide for 2 weeks. Liver CYP1A2 mRNA was measured using reverse transcription-polymerase chain reaction. CYP1A2 protein was detected using immunoblotting. CYP1A2 activity was assayed using high performance liquid chromatography, with caffeine as the CYP1A2 substrate.


RESULTS
CYP1A2 mRNA levels after flutamide treatment at 100 mg/kg and 200 mg/kg were, respectively, 1.86 and 3.11-fold higher than those of the control. Correspondingly, CYP1A2 protein increased 1.78 and 2.89-fold and CYP1A2 activity increased approximately 1.65 and 2.83-fold, respectively, relative to controls. Flutamide treatment at 50 mg/kg had no significant effect on CYP1A2 mRNA, protein, or enzyme activity.


CONCLUSIONS
Giving rats flutamide induced liver CYP1A2 expression in a dose-dependent manner.
Wang
Hai-xue
HX
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, China.
Liu
Xiao
X
Xu
Chang-jiang
CJ
Ma
Xiao-chao
XC
Long
Jian-er
JE
Li
Duan
D
D000726:Androgen Antagonists / Q000633:toxicity; D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005485:Flutamide / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000726:Androgen Antagonists; D012333:RNA, Messenger; D005485:Flutamide; D019388:Cytochrome P-450 CYP1A2