Luotamo M, Elovaara E, Raunio H, Pelkonen O, Riihimäki V, Vainio H
Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki, Finland.
Arch Toxicol. 1991;65(8):661-5. doi: 10.1007/BF02098033.
Tissue distribution and effects induced by 2,2',4,4',5,5'-hexachlorobiphenyl (245-HCB) on cytocrome P450 isozymes were compared with those of 2,2',3,3',6,6'-hexacholorobiphenyl (236-HCB). Male Wistar rats were given a single intragastric dose (23 mg/kg body wt) of either isomer, and killed after 72 h. At termination the tissue concentrations of 245-HCB were considerably higher than those of 236-HCB, suggesting a more effective metabolism of the latter. The binding affinity of 236-HCB to cytochrome P450 was higher and the magnitude of binding greater than of 245-HCB. 245-HCB-treatment elevated the hepatic concentration of cytochrome P450 and also the activities of 7-pentoxyresorufin O-depentylase (50-fold), aniline p-hydroxylase (2-fold) and 7-ethoxycoumarin O-deethylase (2-fold), a response typical of phenobarbital-type inducers. In the Western immunoblot of liver microsomes from 245-HCB treated rats, an increased amount of P450IIB 1/2 was detected by a monoclonal antibody 2-66-3, which specifically detects phenobarbital inducible isoenzymes. The minimum molecular mass of the P450 isozyme induced was 52 kDa. After 236-HCB administration, a weak inducing effect was observed.
比较了2,2',4,4',5,5'-六氯联苯（245-HCB）和2,2',3,3',6,6'-六氯联苯（236-HCB）在组织分布及对细胞色素P450同工酶诱导作用方面的差异。给雄性Wistar大鼠单次灌胃给予任一异构体（23 mg/kg体重），72小时后处死。处死时，245-HCB的组织浓度显著高于236-HCB，提示后者的代谢更有效。236-HCB与细胞色素P450的结合亲和力更高，结合量也大于245-HCB。245-HCB处理可提高细胞色素P450的肝脏浓度，同时提高7-戊氧基试卤灵O-脱戊基酶（50倍）、苯胺对羟基化酶（2倍）和7-乙氧基香豆素O-脱乙基酶（2倍）的活性，这是苯巴比妥型诱导剂的典型反应。在245-HCB处理大鼠肝脏微粒体的Western免疫印迹中，用单克隆抗体2-66-3检测到P450IIB 1/2的量增加，该抗体可特异性检测苯巴比妥诱导的同工酶。诱导产生的P450同工酶的最小分子量为52 kDa。给予236-HCB后，观察到较弱的诱导作用。
