Dent J G, Elcombe C R, Netter K J, Gibson J E
Drug Metab Dispos. 1978 Jan-Feb;6(1):96-101.
Various parameters have been measured in order to characterize the type of cytochrome(s) P-450 induced by a single ip injection of polybrominated biphenyls (PBB's), 150 mg/kg, given to female rats. The ratio of the 427/455-nm peaks in the microsomal ethylisocyanide difference spectra showed a gradual increase with time after treatment with PBB's. Inhibition studies of aryl hydrocarbon hydroxylase and ethoxycoumarin O-de-ethylase and alpha-naphthoflavone and metyrapone also showed changes in the qualitative nature of these enzymes after treatment with PBB's. Both the high- and low-affinity KM values for ethoxycoumarin O-de-ethylase decreased in magnitude from 0.240 and 0.083 micrometer at 24 hr to 0.188 and 0.042 micrometer, respectively, at 192 hr after treatment with PBB's. Sodium dodecyl sulfate-gel electrophoresis failed to demonstrate a 3-methylcholanthrene-like pattern of hemoprotein at any time after treatment with PBB's. We conclude that while PBB's have some of the properties of a mixed inducer they do not have all of the properties of both phenobarbital and 3-methylcholanthrene, and the PBB's may represent a new class of inducing agents.
为了表征单次腹腔注射150mg/kg多溴联苯(PBBs)给雌性大鼠后诱导产生的细胞色素P-450的类型,已对各种参数进行了测量。微粒体乙基异氰化物差示光谱中427/455nm峰的比值在PBBs处理后随时间逐渐增加。芳烃羟化酶、乙氧香豆素O-脱乙基酶以及α-萘黄酮和甲吡酮的抑制研究也表明,PBBs处理后这些酶的性质发生了定性变化。乙氧香豆素O-脱乙基酶的高亲和力和低亲和力KM值在PBBs处理后24小时分别为0.240和0.083微米,在192小时时分别降至0.188和0.042微米。十二烷基硫酸钠凝胶电泳在PBBs处理后的任何时间都未能显示出血红蛋白的3-甲基胆蒽样模式。我们得出结论,虽然PBBs具有混合诱导剂的一些特性,但它们并不具备苯巴比妥和3-甲基胆蒽的所有特性,PBBs可能代表一类新的诱导剂。