To study the regulation of drug-metabolizing activities associated to cytochromes P-450 we investigated the effects of hexobarbital to the specific cytochromes P-450 dependent monooxygenase activities and the level of P450IA1 and P450IIB1/IIB2 mRNAs according to culture time. We found that the addition of hexobarbital to culture medium increased ethoxycoumarin O-deethylase, aniline 4-hydroxylase and ethoxyresorufin O-deethylase activities. In constrast, penthoxyresorufin O-dealkylase activity and the level of each specific mRNA were not increased.
The fact that the induction of enzyme activities does not parallel the concentration of mRNA indicates the regulation of cytochromes P-450 in culture is brought about by mechanisms involving transcriptional, translational and post-translational regulation.
본 연구에서는 백쥐 간세포의 일차 배양에서 hexobarbital에 의한 특정 약물 대사효소가 유지되는 기작을 연구하였다. Hexobarbital을 배양초기에 처리하였을 때 ethoxycoumarin O-deethylase, aniline 4-hydroxylase, 와 ethoxyresorufin O-deethylase의 활성도는 생체와 같은 수준으로 증가시켰다. 반면 penthoxyresorufin O-dealkylase 활성도와 P450IA1과 P450IIB1/IIB2 mRNA 수준은 대조군과 차이없이 생체와 같은 수준으로 유지되었다. 위의 결과들로 보아 hexobarbital에 의한 약물 대사능 유지는 mRNA 수준과 일치하지 않는 것으로 생각된다.
