Yang T C, Georgy K A, Mei M, Durante M, Craise L M
Radiation Biophysics Laboratory, NASA Johnson Space Center, Houston, TX 77058, USA.
ASGSB Bull. 1995 Oct;8(2):106-12.
Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic mechanism(s) of radiogenic transformation of human epithelial cells.
辐射致癌是太空旅行风险评估中被认为重要的主要生物学效应之一。包括培养细胞和动物在内的各种生物学模型系统已被证明对研究太空辐射的致癌作用有用，太空辐射由高能电子、质子和重离子组成。培养中研究肿瘤细胞转化技术的发展使得研究辐射致癌的细胞和分子机制成为可能。因此，培养细胞系统是动物模型的补充。许多研究者已确定了电离辐射和非电离辐射在培养的哺乳动物细胞中的致癌作用。辐射转化研究最常使用的细胞系统之一是小鼠胚胎细胞（C3H10T1/2），这种细胞易于培养，并能给出良好的定量剂量反应曲线。利用该细胞系统已获得了不同能量和线能量转移（LET）的重离子的相对生物学效应（RBE）。研究者在其他细胞系统中也观察到了类似的RBE与LET关系。除了RBE测量外，关于亚致癌和潜在致癌损伤的修复、直接和间接效应、主要靶点和损伤、细胞间相互作用的重要性以及癌基因和肿瘤抑制基因在辐射致癌中的作用等基本问题也已得到研究，并取得了有趣的结果。最近已开发出几种人类上皮细胞系统，并且已证明电离辐射可使这些细胞发生转化。然而，这些细胞的致癌转化需要较长的表达时间和/或多次辐射暴露。有限的实验数据表明，高LET重离子在诱导细胞转化方面可能比低LET辐射更有效。对克隆的转化体进行细胞遗传学和分子分析，可深入了解人类上皮细胞辐射转化的基本遗传机制。
