Huang S, Gibson G G
Department of Biochemistry, University of Surrey, Guildford, England, United Kingdom.
Toxicol Appl Pharmacol. 1991 Mar 15;108(1):86-95. doi: 10.1016/0041-008x(91)90271-f.
Differential induction of hepatic cytochromes P450 by 3,4,5,3',4'-pentachlorobiphenyl (PENCB) has been observed in the rat and the guinea pig: (1) in rat and guinea pig, treatment with the chosen dose levels resulted in significant induction of total, carbon monoxide-discernible cytochrome P450 content; the absorption maximum of the CO-adduct of the dithionite-reduced microsomes from PENCB-induced rat liver was shifted from 450 to 448 nm, whereas its counterpart in the guinea pig did not; (2) PENCB treatment significantly increased EROD activity in rat liver microsomes (up to 60-fold), but the increase in the guinea pig was less than fivefold; (3) PENCB-induced rat liver microsomes significantly induced the omega-1 hydroxylation of arachidonic acid (AA); however, omega-1 hydroxylation of AA was hardly affected by PENCB treatment in the guinea pig. Instead, omega-hydroxylation was significantly increased in this latter species. In addition to omega-1 hydroxylation in the rat or omega-hydroxylation in the guinea pig, an additional AA metabolite (designated peak III) was significantly induced by PENCB in both rat and guinea pig; (4) Western blot and ELISA analyses with polyclonal anti-P450 IA1/IA2 and IVA1 antibodies demonstrated that P450 IA1 was significantly induced in the rat but only slightly induced in the guinea pig, whereas P450 IVA1 was significantly suppressed in the rat but significantly induced in the guinea pig by PENCB treatment. The induction of the third arachidonic acid metabolite peak, Peak III, in both rat and guinea pig, particularly in the guinea pig, is obviously neither mediated by P450 IA1 nor by P450 IV A1. At present, it is still unclear which form(s) of cytochrome P450 isoenzymes is responsible for this latter hydroxylation of arachidonic acid.
在大鼠和豚鼠中观察到3,4,5,3',4'-五氯联苯（PENCB）对肝细胞色素P450的诱导存在差异：（1）在大鼠和豚鼠中，采用选定剂量水平进行处理可导致总一氧化碳可识别的细胞色素P450含量显著诱导；PENCB诱导的大鼠肝脏连二亚硫酸盐还原微粒体的CO加合物的吸收最大值从450nm移至448nm，而豚鼠中的对应值未发生移动；（2）PENCB处理显著增加大鼠肝脏微粒体中的EROD活性（高达60倍），但豚鼠中的增加幅度小于五倍；（3）PENCB诱导的大鼠肝脏微粒体显著诱导花生四烯酸（AA）的ω-1羟基化；然而，PENCB处理对豚鼠中AA的ω-1羟基化几乎没有影响。相反，在后者中ω-羟基化显著增加。除了大鼠中的ω-1羟基化或豚鼠中的ω-羟基化外，PENCB在大鼠和豚鼠中均显著诱导了另一种AA代谢物（称为峰III）；（4）用多克隆抗P450 IA1/IA2和IVA1抗体进行的蛋白质免疫印迹和酶联免疫吸附测定分析表明，P450 IA1在大鼠中显著诱导，但在豚鼠中仅轻微诱导，而PENCB处理使大鼠中的P450 IVA1显著抑制，但在豚鼠中显著诱导。大鼠和豚鼠中，尤其是豚鼠中，第三种花生四烯酸代谢物峰（峰III）的诱导显然既不是由P450 IA1介导，也不是由P450 IV A1介导。目前，仍不清楚哪种细胞色素P450同工酶形式负责花生四烯酸的后一种羟基化。
