Lechner M C, Ribeiro V L, Henrique D, Barroso M, Cravino M M
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Bull Cancer. 1990;77(5):509-14.
The adaptive response of the liver to phenobarbital is characterized by a strong cell hypertrophy and coordinate induction of specific P450 forms (IIB1, 2; IIC7, IIIA1). The pattern of active mRNA is significantly changed, demonstrating the establishment of PB phenotype. Employed as a promoting agent in experimental hepatocarcinogenesis, PB triggers a significantly different, uncoordinated response. Only P450 IIB1 is positively modulated while P450 IIC7 mRNA becomes repressed. Mechanisms underlying the differential P450 adaptative response to PB in the initiated versus non-initiated liver are discussed in the light of both the importance of epigenetic events and the possible role of P450 mono-oxygenases in hepatocarcinogenic promotion by PB.
肝脏对苯巴比妥的适应性反应的特征是强烈的细胞肥大以及特定细胞色素P450亚型(IIB1、2;IIC7、IIIA1)的协同诱导。活性mRNA的模式发生显著变化,表明苯巴比妥表型的建立。在实验性肝癌发生过程中用作促癌剂时,苯巴比妥引发了明显不同的、不协调的反应。只有细胞色素P450 IIB1受到正向调节,而细胞色素P450 IIC7 mRNA则受到抑制。鉴于表观遗传事件的重要性以及细胞色素P450单加氧酶在苯巴比妥促肝癌作用中的可能作用,讨论了起始肝脏与未起始肝脏中细胞色素P450对苯巴比妥的差异性适应性反应的潜在机制。