Machala M, Mátlová L, Nezveda K, Turánek J, Horavová P, Granátová M, Nevoránková Z
Veterinary Research Institute, Brno, Czech Republic.
Vet Med (Praha). 1995 Oct;40(10):327-32.
Cytochromes P450-dependent monooxygenase activities were determined and compared in mouse liver microsomes and in hepatoma cell homogenates after exposure to prototype inducers of individual P450 enzymes. In vivo inductions of levels of mouse hepatic monooxygenase activities have been found as effective biochemical markers of toxicity potentials of a series of classes of xenobiotics (CYP1A induction for toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, coplanar polychlorinated biphenyls, polycyclic aromatic hydrocarbons and related pollutants; CYP2E induction for dialkylnitrosamines and organic solvents, e.g. acetone and ethanol; CYP2B and CYP3A induction for phenobarbital- and dexamethasone-type of xenobiotics). A specific induction of CYP1A-dependent O-dealkylase activities by TCDD was found in Hepa-1 and Hep G2 cell cultures, but no in vitro induction of other P450 enzymes was found after the treatment with phenobarbital, acetone or dexamethasone. Therefore, mouse liver is a suitable in vivo system for the testing of inducing effects of xenobiotics on all relevant P450 forms, while hepatoma cell cultures are usable only for the bioassay of TCDD-like toxicity.
在暴露于单个细胞色素P450酶的原型诱导剂后,测定并比较了小鼠肝微粒体和肝癌细胞匀浆中的细胞色素P450依赖性单加氧酶活性。已发现小鼠肝脏单加氧酶活性水平的体内诱导是一系列外源化合物毒性潜力的有效生化标志物(CYP1A诱导用于2,3,7,8-四氯二苯并-对-二恶英、共平面多氯联苯、多环芳烃及相关污染物的毒性作用;CYP2E诱导用于二烷基亚硝胺和有机溶剂,如丙酮和乙醇;CYP2B和CYP3A诱导用于苯巴比妥和地塞米松类型的外源化合物)。在Hepa-1和Hep G2细胞培养物中发现TCDD对CYP1A依赖性O-脱烷基酶活性有特异性诱导,但在用苯巴比妥、丙酮或地塞米松处理后未发现其他P450酶的体外诱导。因此,小鼠肝脏是用于测试外源化合物对所有相关P450形式诱导作用的合适体内系统,而肝癌细胞培养仅可用于TCDD样毒性的生物测定。