Effect of in vitro and in vivo treatment with mitomycin C on activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver.
OBJECTIVE
To evaluate the effect of in vitro and in vivo treatment with mitomycin C (MMC) on activities of CYP2D1/2, CYP2C1 , and CYP1A2 in the liver of male rats.


METHODS
Using HPLC to determine the activities of the three isoenzymes in rat liver microsomes by detecting the specific metabolites of their substrates after treatment with inducers in vivo or inhibitors in vitro.


RESULTS
In vitro, MMC inhibited the activity of CYP2D1/2, CYP2C11, and CYP1A2 in dexamethasone-induced microsomes by (19 +/- 6)% (P < 0.05), (85 +/- 10)% (P < 0.01), and (36 +/- 6)% (P < 0.05), respectively, and decreased the activity of CYP1A2 in beta-naphthoflavone-induced microsomes by (58 +/- 6)% (P < 0.01). Rats were injected intraperitoneally with 20% of the LD50 of MMC for 3 or 6 d. The treatment showed no significant effect on microsomal activities of CYP2D1/2, CYP2C11 or CYP1A2.


CONCLUSIONS
MMC can inhibit the activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver microsomes in vitro, but it showed no significant effect on the activities of the three isoenzymes in vivo.
Hao
Fu-Rong
FR
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
Yan
Min-Fen
MF
Tong
Shun-Gao
SG
Xu
Li-Ming
LM
Jn
Yi-Zun
YZ
D000429:Alcohol Oxidoreductases; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001711:Biotransformation; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D016685:Mitomycin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D039181:Steroid 16-alpha-Hydroxylase / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin; D000429:Alcohol Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C504568:Cyp2d1 protein, rat; D019388:Cytochrome P-450 CYP1A2; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase