Ternell M, Lönnroth C, Lundholm K
Am J Physiol. 1985 Nov;249(5 Pt 1):E461-9. doi: 10.1152/ajpendo.1985.249.5.E461.
This study has evaluated changes in RNA synthesis in livers under the distant influence of a malignant tumor. A transplantable-induced sarcoma (MCG 101), transplanted on inbred adult mice (C57BL/6J), was used. Activities of DNA-dependent RNA polymerase (EC 2.7.7.6) were measured in relation to RNA content and translational activity. Liver nuclei from freely fed sarcoma-bearing mice had increased RNA synthesis. As a consequence of this, RNA content per DNA was increased in liver tissue. This was independent of depressed food intake and malnutrition. Elevated RNA synthesis, proportional to the tumor burden was due to an increased proportion of chromatin-engaged RNA polymerase I and II activities. RNA polymerase III activity (template-engaged form) was unchanged when evaluated in isolated nuclei, but appeared to be increased in partially purified extracts of nuclei. RNA content in tumor-host liver was a composite of increased levels of rRNA and tRNA, whereas the levels of poly(A)+ mRNA could not be measured as increased. Overall translational activities in vitro of mRNA from liver tissue of tumor-bearing, pair-weighed, and freely fed tumor-free controls were qualitatively and quantitatively different. mRNA from tumor-bearing mice directed an increased synthesis, particularly of larger proteins (above 55,000 daltons) compared with control animals. The results support the conclusion that previous evidence of elevated net protein synthesis in tumor-host liver is accompanied by increased transcription of genes coding for RNA and also for some or several hepatic proteins.
本研究评估了在恶性肿瘤的远距离影响下肝脏中RNA合成的变化。使用了移植到近交成年小鼠(C57BL/6J)体内的可移植诱导肉瘤(MCG 101)。测定了依赖DNA的RNA聚合酶(EC 2.7.7.6)的活性与RNA含量及翻译活性的关系。来自自由进食的荷瘤小鼠的肝细胞核RNA合成增加。因此,肝组织中每单位DNA的RNA含量增加。这与食物摄入量减少和营养不良无关。与肿瘤负荷成比例的RNA合成升高是由于与染色质结合的RNA聚合酶I和II活性比例增加。在分离的细胞核中评估时,RNA聚合酶III活性(模板结合形式)未发生变化,但在细胞核的部分纯化提取物中似乎有所增加。肿瘤宿主肝脏中的RNA含量是rRNA和tRNA水平升高的综合结果,而聚腺苷酸加尾mRNA的水平未检测到增加。荷瘤、配对称重和自由进食的无瘤对照小鼠肝脏组织mRNA的体外总体翻译活性在定性和定量上均有所不同。与对照动物相比,荷瘤小鼠的mRNA指导合成增加,尤其是较大蛋白质(高于55,000道尔顿)的合成增加。这些结果支持以下结论:先前关于肿瘤宿主肝脏净蛋白质合成升高的证据伴随着编码RNA以及某些或几种肝脏蛋白质的基因转录增加。