Blaich G, Göttlicher M, Cikryt P, Metzler M
Institute of Toxicology and Pharmacology, University of Würzburg, F.R.G.
Chem Biol Interact. 1988;67(1-2):129-38. doi: 10.1016/0009-2797(88)90092-0.
The activities of 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-deethylase (PROD), 7-ethoxycoumarin-O-deethylase (ECOD) and aromatic hydrocarbon hydroxylase (AHH) were measured in hepatic microsomes from male and female Wistar rats and Syrian golden hamsters in order to probe the basal activity and the inducibility by phenobarbital (PB) and 3-methylcholanthrene (MC) of different P-450 isoenzymes. The basal activities of EROD and ECOD, but not PROD and AHH, were higher in male hamsters than in male rats. No sex-related difference in enzyme activities was observed with hamsters, whereas male rats had a higher ECOD and AHH activity than female rats. Induction by PB led to a 450-fold and 250-fold increase in PROD activity in male and female rat liver microsomes, respectively, while MC had a more pronounced inductive effect on EROD activity in this species. In hamsters, EROD activity was induced by MC but not by PB. Unexpectedly PROD activity in male and female hamster liver microsomes was only moderately induced by PB, the extent being lower than on induction by MC. Therefore, the activity of PROD, which is useful as a specific enzymatic assay for P-450 IIB in the rat liver, cannot be used to probe PB-like inducers in the hamster liver.
为了探究不同P-450同工酶的基础活性以及苯巴比妥(PB)和3-甲基胆蒽(MC)的诱导性,我们测定了雄性和雌性Wistar大鼠及叙利亚金黄地鼠肝脏微粒体中7-乙氧基试卤灵-O-脱乙基酶(EROD)、7-戊氧基试卤灵-O-脱乙基酶(PROD)、7-乙氧基香豆素-O-脱乙基酶(ECOD)和芳烃羟化酶(AHH)的活性。雄性地鼠中EROD和ECOD的基础活性高于雄性大鼠,而PROD和AHH的基础活性则不然。在地鼠中未观察到酶活性的性别相关差异,而雄性大鼠的ECOD和AHH活性高于雌性大鼠。PB诱导导致雄性和雌性大鼠肝脏微粒体中PROD活性分别增加450倍和250倍,而MC对该物种的EROD活性具有更显著的诱导作用。在地鼠中,EROD活性由MC诱导而非PB。出乎意料的是,PB仅适度诱导雄性和雌性地鼠肝脏微粒体中的PROD活性,其程度低于MC诱导的程度。因此,PROD活性在大鼠肝脏中可作为P-450 IIB的特异性酶测定方法,但不能用于检测地鼠肝脏中的PB样诱导剂。