Celier C, Cresteil T
INSERM U 75, C.H.U. Necker, Paris, France.
Biochem Pharmacol. 1989 Sep 1;38(17):2825-32. doi: 10.1016/0006-2952(89)90437-1.
Response of congenitally jaundiced rats (Gunn rats) to administration of polycyclic aromatic hydrocarbons (PAH) was investigated and compared to that of Wistar rats. Unlike Wistar, Gunn males did not exhibit changes in the overall cytochrome P-450 content of hepatic microsomes. The first step in the induction process (i.e. presence of cytosolic receptors for PAH) was found present and functionally similar (number of sites, Kd) to that of Wistar rats from which the Gunn strain is derived. An increase in monooxygenase activities related to P-450c and P-450d isoenzymes specifically induced by PAH was noticed, whereas no effect could be detected on the glucuronidation rate of either 4-nitrophenol, testosterone or estrone. As determined by immunoquantification after Western blotting, the isoenzymatic profile of P-450 from PAH-treated male Gunn rats showed an increase of P-450c and P-450d accompanied by an equivalent decrease in P-4502c (major male-specific isoenzyme). The balance between increase in P-450c and P-450d and decrease in P-4502c may explain the absence of increase in the total P-450 in PAH-treated male Gunn rats. Such a response was not observed in PAH-treated male Wistar rats or in female rats of both strains. In contrast, the response of male Gunn rats to PB treatment was similar to that observed in Wistar rats, i.e. increase in overall cytochrome P-450 content of hepatic microsomes and of specific isoenzyme P-450b/e. A possible regulation of P-450 isoenzyme synthesis by the intracellular haem pool might be involved.
研究了先天性黄疸大鼠（冈恩大鼠）对多环芳烃（PAH）给药的反应，并与Wistar大鼠进行了比较。与Wistar大鼠不同，冈恩雄性大鼠肝微粒体的总体细胞色素P-450含量未表现出变化。发现诱导过程的第一步（即PAH的胞质受体的存在）与冈恩品系所源自的Wistar大鼠的情况相同，在功能上相似（位点数量、解离常数）。注意到与PAH特异性诱导的P-450c和P-450d同工酶相关的单加氧酶活性增加，而对4-硝基苯酚、睾酮或雌酮的葡萄糖醛酸化率未检测到影响。通过蛋白质免疫印迹后的免疫定量测定，PAH处理的雄性冈恩大鼠的P-450同工酶谱显示P-450c和P-450d增加，同时P-4502c（主要的雄性特异性同工酶）等量减少。P-450c和P-450d的增加与P-4502c的减少之间的平衡可能解释了PAH处理的雄性冈恩大鼠中总P-450未增加的原因。在PAH处理的雄性Wistar大鼠或两个品系的雌性大鼠中未观察到这种反应。相比之下，雄性冈恩大鼠对PB处理的反应与Wistar大鼠中观察到的反应相似，即肝微粒体的总体细胞色素P-450含量和特异性同工酶P-450b/e增加。细胞内血红素池可能参与了P-450同工酶合成的可能调节。
