The phenotypic response of rat liver to a carcinogenic protocol involving initiation/selection and promotion with and without phenobarbital (PB) feeding was studied in pubertal and adult male rats. Considering the early presence of preneoplastic nodular areas, it appeared that pubertal rats, initiated at 6-7 weeks, presented a higher susceptibility to the protocol than adult rats initiated at 9-10 weeks. Altered liver phenotype was characterized by: (1) gamma-glutamyl-transpeptidase (GGT) and glutathione S-transferase (GST) activities; (2) the expression of two forms of cytochrome P-450; de novo PB-inducible P-450 II B 1,2 and P-450 II C 7 normally expressed in 45-day-old rats and PB-inducible, and (3) the expression of albumin and alpha-fetoprotein cDNAs. In the absence of PB, the susceptibility of pubertal rat liver to hepatocarcinogenesis was related to a special metabolic phenotype enriched in GGT and GST activities by comparison with the quasi-normal expression of both P-450s. Adult rat liver presented a less altered pattern closer to that of noninitiated rat liver. During PB promotion, the loss of PB inducibility of P-450 II C 7 in pubertal rat liver suggested that the hormonal status of the animals could interact with initiation to modulate specific gene expression. The late phase of PB promotion revealed the loss of highly differentiated functions (P-450s, albumin), whereas enzymatic markers associated with preneoplastic foci showed a persistent high expression.

译文

:在青春期和成年雄性大鼠中研究了大鼠肝脏对涉及开始/选择和促进(有或没有苯巴比妥(PB)喂养)致癌方案的表型反应。考虑到肿瘤前结节区域的早期存在,看来与在9-10周龄开始的成年大鼠相比,在6-7周龄开始的青春期大鼠对方案的敏感性更高。肝表型改变的特征是:(1)γ-谷氨酰转肽酶(GGT)和谷胱甘肽S-转移酶(GST)活性; (2)两种形式的细胞色素P-450的表达;从头开始PB诱导的P-450 II B 1,2和P-450 II C 7在45天大的大鼠中正常表达,并且在PB诱导中正常表达,以及(3)白蛋白和甲胎蛋白cDNA的表达。在没有PB的情况下,与两个P-450的准正常表达相比,青春期大鼠肝脏对肝癌发生的敏感性与富含GGT和GST活性的特殊代谢表型有关。成年大鼠肝脏的变化较小,与未启动大鼠肝脏的变化较小。在PB促进过程中,青春期大鼠肝脏中P-450 II C 7的PB诱导能力丧失,表明动物的荷尔蒙状态可能与启动相互作用,从而调节特定基因的表达。 PB促进的晚期阶段揭示了高度分化的功能(P-450s,白蛋白)的丧失,而与肿瘤前病灶相关的酶标记物显示了持续的高表达。

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