Diehl A M, Bisgaard H C, Kren B T, Steer C J
Department of Medicine, Veterans Affairs Medical Center, Washington D.C. 20422.
Hepatology. 1991 Apr;13(4):722-7.
The effects of chronic ethanol consumption on enzyme systems involved in carcinogen activation and detoxification were studied in a rat model of liver regeneration. In control rats, steady-state messenger RNAs of cytochrome P450j decreased 12 to 24 hr after partial hepatectomy but were fully recovered by 48 to 72 hr. In contrast, messenger RNA levels of cytochrome P450b and P450d did not vary significantly during that period. Steady-state messenger RNA levels for the placental form of glutathione S-transferase decreased within 30 min after partial hepatectomy but fluctuated until levels returned to normal by 48 hr. Preliminary nuclear run-on analyses suggest that the regulation of cytochrome P450j and the placental form of glutathione S-transferase messenger RNA levels involves posttranscriptional control in these animals. In ethanol-fed rats, as in controls, expression of cytochrome P450j and the placental form of glutathione S-transferase decreased transiently after partial hepatectomy. However, compared with control values, messenger RNA levels for cytochrome P450j were greater in ethanol-fed rats at each time point. Similar results were noted for placental glutathione S-transferase levels from 12 to 48 hr after partial hepatectomy. Ethanol feeding had no apparent effect on steady-state messenger RNA levels of cytochrome P450d, P450b or the multidrug-resistant gene. In both ethanol and control rats, only prehepatectomy levels of cytochrome P450 transcripts correlated with levels of the respective P450 isoenzymes. These data indicate that liver regeneration selectively decreases the steady-state messenger RNA expression of certain isoenzymes of cytochrome P450 and glutathione S-transferase.(ABSTRACT TRUNCATED AT 250 WORDS)
在肝再生大鼠模型中，研究了长期乙醇摄入对参与致癌物激活和解毒的酶系统的影响。在对照大鼠中，细胞色素P450j的稳态信使核糖核酸在部分肝切除术后12至24小时下降，但在48至72小时完全恢复。相比之下，细胞色素P450b和P450d的信使核糖核酸水平在此期间无显著变化。胎盘型谷胱甘肽S-转移酶的稳态信使核糖核酸水平在部分肝切除术后30分钟内下降，但波动直至48小时恢复正常。初步的核转录分析表明，细胞色素P450j和胎盘型谷胱甘肽S-转移酶信使核糖核酸水平的调节涉及这些动物的转录后控制。在乙醇喂养的大鼠中，与对照大鼠一样，部分肝切除术后细胞色素P450j和胎盘型谷胱甘肽S-转移酶的表达短暂下降。然而，与对照值相比，乙醇喂养大鼠在每个时间点的细胞色素P450j信使核糖核酸水平更高。部分肝切除术后12至48小时的胎盘谷胱甘肽S-转移酶水平也有类似结果。乙醇喂养对细胞色素P450d、P450b或多药耐药基因的稳态信使核糖核酸水平无明显影响。在乙醇喂养和对照大鼠中，只有肝切除术前细胞色素P450转录本水平与各自的P450同工酶水平相关。这些数据表明，肝再生选择性地降低了细胞色素P450和谷胱甘肽S-转移酶某些同工酶的稳态信使核糖核酸表达。（摘要截短于250字）
