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人类细胞系对小剂量的放射敏感性。有一些临床意义吗?

Radiosensitivity of human cell lines to small doses. Are there some clinical implications?

作者信息

Malaise E P, Lambin P, Joiner M C

机构信息

Laboratoire de Radiobiologie Cellulaire (Unité Inserm 247), Institut Gustave-Roussy, Villejuif, France.

出版信息

Radiat Res. 1994 Apr;138(1 Suppl):S25-7.

PMID:8146319
Abstract

The concept of intrinsic radiosensitivity is now strongly associated with the linear-quadratic (LQ) model which is currently the best and the most reliable method to fit the first three decades of a survival curve for both human fibroblast and human tumor cell lines. This approach has led to the major conclusions that it is the initial part, and not the distal part, of the survival curve which truly characterizes intrinsic cellular radiosensitivity and there is a correlation between the parameters describing mainly the initial part of the survival curve (alpha, SF2, D) and the clinical radioresponsiveness. More accurate analysis with flow cytometry or a dynamic microscopic image processing scanner (DMIPS) has allowed further study of the survival curve which has shown two sorts of substructure. On one hand, the overall survival curve of exponentially growing cells is described by two or more sets of alpha, beta parameters (heterogeneity in radiosensitivity due to the cell cycle). On the other hand, hypersensitivity at very low doses (< 0.5 Gy) followed by an increase of the radioresistance of the whole population at higher doses has also been observed. This phenomenon is not described by the conventional LQ model and has been interpreted as an induced radioresistance which seems to be negatively correlated with intrinsic radiosensitivity. In clinical radiotherapy, there are two sorts of response of normal tissues: (1) the early and late damage and (2) the carcinogenesis. Concerning the first point, the clinically detectable radiation damage appears at doses usually around 20 Gy (in 2-Gy fractions) with the exception of the hemopoietic and the lymphatic tissues. Therefore, the small doses delivered at the edges or in the penumbrae of treatment fields in routine radiotherapy cannot create detectable damage, despite a potentially much higher effect per unit dose, because the total doses are still very small. However, it may be important to bear in mind the possible extra effect of low doses outside the target volume if regions in the vicinity are subsequently retreated. Concerning clinical radiation-induced carcinogenesis, three studies described a higher relative risk associated with small doses per fraction or very low dose rate. The results and the interpretation of these studies are discussed.

摘要

内在放射敏感性的概念现在与线性二次(LQ)模型紧密相关,该模型是目前拟合人类成纤维细胞和人类肿瘤细胞系生存曲线前三十年的最佳且最可靠的方法。这种方法得出了主要结论,即真正表征细胞内在放射敏感性的是生存曲线的起始部分而非末端部分,并且描述生存曲线起始部分的参数(α、SF2、D)与临床放射反应性之间存在相关性。使用流式细胞术或动态显微镜图像处理扫描仪(DMIPS)进行的更精确分析,使得对生存曲线有了进一步研究,结果显示出两种亚结构。一方面,指数生长细胞的总体生存曲线由两组或更多组的α、β参数描述(由于细胞周期导致的放射敏感性异质性)。另一方面,也观察到在非常低的剂量(<0.5 Gy)下出现超敏感性,随后在较高剂量下整个群体的放射抗性增加。这种现象无法用传统的LQ模型描述,并且被解释为一种诱导的放射抗性,它似乎与内在放射敏感性呈负相关。在临床放射治疗中,正常组织有两种反应:(1)早期和晚期损伤;(2)致癌作用。关于第一点,除造血和淋巴组织外,临床上可检测到的放射损伤通常在剂量约为20 Gy(分2 Gy分次)时出现。因此,在常规放射治疗中,治疗野边缘或半影区给予的小剂量,尽管每单位剂量的潜在效应可能高得多,但由于总剂量仍然非常小,不会产生可检测到的损伤。然而,如果随后对附近区域进行再次治疗,记住靶体积外低剂量可能产生的额外效应可能很重要。关于临床放射诱导的致癌作用,三项研究描述了与低分次剂量或非常低剂量率相关的较高相对风险。对这些研究的结果和解释进行了讨论。

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