Inducible repair and the two forms of tumour hypoxia - Time for a paradigm shift
Inducible repair and the two forms of tumour hypoxia - Time for a paradigm shift
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DOI：
10.1080/028418699432590
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发表时间：
1999-01-01
期刊：
影响因子：
3.1
通讯作者：
Dasu, A
中科院分区：
文献类型：
--
作者：
Denekamp, J;Dasu, A
临床经验表明，在60和70戈伊之间存在一个治疗窗口，其中许多肿瘤被根除，但邻近正常组织的功能被保留。这意味着肿瘤中的细胞杀伤比正常组织中可接受的要多得多。需要0.5或更低的SF2来消除所有肿瘤细胞。而需要0.8或更高的SF2来解释为什么这些剂量被正常组织耐受。在氧合良好的正常细胞和肿瘤细胞的内在敏感性之间没有这种系统性差异。谣言中存在的耐辐射缺氧细胞使人们更难理解临床上的成功。然而，有实验证据表明，饥饿的细胞失去了他们的修复能力，作为细胞能量chargr的耗尽的结果。MRS研究表明，低ATP水平是啮齿动物和man.In本文中的实体瘤的一个特征，我们将在饥饿，慢性缺氧的细胞修复无能的概念。这种细胞的敏感性增加来自对显示可诱导修复的哺乳动物细胞系的分析。它与SF2成正比，在抗性细胞中最高。急性低氧辐射抗性细胞和慢性低氧辐射敏感细胞之间的区别提供了成功的放射治疗的现实建模的关键。它还为放射治疗开辟了新的概念方法。我们的结论是，它是必要的，以区分这两种缺氧细胞的预测分析和模型。
Clinical experience shows that there is a therapeutic window between 60 and 70 Gy where many tumours are eradicated, but the function of the adjacent normal tissues is preserved. This implies much more cell kill in the: tumour than is acceptable in the normal tissue. An SF2 of 0.5 or lower is needed to account for the eradication of all tumour cells. while an SF2 of 0.8 or higher is needed to explain why these doses are tolerated by normal tissues. No such systematic difference is known between the intrinsic sensitivity of well-oxygenated normal and tumour cells. The presence of radioresistant hypoxic cells in rumours makes it even more difficult ro understand the clinical success. However, there is experimental evidence that starved cells lose their repair competence as a result of the depletion of cellular energy char gr. MRS studies have shown that low ATP levels are a characteristic feature of solid tumours in rodents and man. In this paper we incorporate the concept of repair incompetence in starving, chronically hypoxic cells. The increased sensitivity of such cells has been derived From an analysis of mammalian cell lines showing inducible repair. It is proportional to the SF2 and highest in resistant cells. Thr distinction between acutely hypoxic radioresistant cells and chronically hypoxic radiosensitive cells provides the key to the realistic modelling of successful radiotherapy. It also opens new conceptual approaches to radiotherapy. We conclude that it is essential to distinguish between these two kinds of hypoxic cells in predictive assays and models.