Lechner M C, Barroso M, Decloitre F, Lafarge-Frayssinet C, Ouldelhkim M, Frayssinet C
Laboratório de Bioquímica, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Biochim Biophys Acta. 1990 Oct 23;1087(2):157-64. doi: 10.1016/0167-4781(90)90200-l.
P-450 IIC7 and IIIA2 mRNAs are constitutively expressed in the hepatic tissue under developmental control. Both forms--as well as IIIA1, 90% homologous to IIIA2 mRNA--display positive modulation by phenobarbital a prototype inducer of the liver monooxygenases and a strong promoter of experimental chemical hepatocarcinogenesis. In the present work the variations in the concentration of these P-450 mRNA were studied in rats submitted to the hepatocarcinogenic protocol of Solt and Farber. We demonstrate that a decrease in the relative concentrations of P-450 IIC7 and IIIA1, 2 mRNA is set up along the tumor promotion stage. Animals--starting the experimental carcinogenic protocol at pubertal age--show a partial inhibition of the physiological expression of P-450 IIIA1,2 mRNA associated to male sex maturation. Administration of phenobarbital results in an acceleration of the pre-neoplastic process which is concomitant with an induction of P-450 IIC7 as well as IIIA1,2 at the earlier promotion stages. P-450 mRNA concentration markedly decreases as the preneoplastic process develops. While an impaired P-450 IIIA1,2 mRNA relative abundance is observed, an inversion of the modulation of P-450 IIC7 as well as of the male phenotype marker alpha-2u-globulin mRNA arises as the tumor promotion stage progresses, both mRNA becoming repressed in response to phenobarbital.
P-450 IIC7和IIIA2信使核糖核酸在发育控制下于肝组织中组成性表达。这两种形式——以及与IIIA2信使核糖核酸有90%同源性的IIIA1——都受到苯巴比妥的正向调节，苯巴比妥是肝脏单加氧酶的典型诱导剂，也是实验性化学致癌作用的强效促进剂。在本研究中，在接受索尔特和法伯肝癌致癌方案的大鼠中研究了这些P-450信使核糖核酸浓度的变化。我们证明，在肿瘤促进阶段，P-450 IIC7和IIIA1、2信使核糖核酸的相对浓度会降低。在青春期开始实验致癌方案的动物显示，与雄性性成熟相关的P-450 IIIA1、2信使核糖核酸的生理表达受到部分抑制。给予苯巴比妥会加速癌前病变过程，这与在早期促进阶段诱导P-450 IIC7以及IIIA1、2同时发生。随着癌前病变过程的发展，P-450信使核糖核酸浓度显著降低。虽然观察到P-450 IIIA1、2信使核糖核酸的相对丰度受损，但随着肿瘤促进阶段的进展，P-450 IIC7以及雄性表型标志物α-2u球蛋白信使核糖核酸的调节发生反转，两种信使核糖核酸在苯巴比妥作用下均受到抑制。
