Effect of in vitro and in vivo treatment with mitomycin C on activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver

AimTo evaluate the effect of in vitro and in vivo treatment with mitomycin C (MMC) on activities of CYP2D1/2, CYP2C11, and CYP1A2 in the liver of male rats. MethodsUsing 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. Resultsin 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 β-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. ConclusionMMC 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.