The molecular and cellular basis of radiosensitivity: implications for understanding how normal tissues and tumors respond to therapeutic radiation.
The molecular and cellular basis of radiosensitivity: implications for understanding how normal tissues and tumors respond to therapeutic radiation.
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DOI：
10.1080/07357909909011718
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发表时间：
1999
影响因子：
2.4
通讯作者：
E. Rosen;S. Fan;S. Rockwell;I. Goldberg
中科院分区：
文献类型：
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作者：
E. Rosen;S. Fan;S. Rockwell;I. Goldberg
我们概述了最近的研究，这些研究极大地扩展了我们对决定电离辐射敏感性或抵抗性的分子和细胞机制的认识。这些知识大部分是通过研究肿瘤和非肿瘤细胞类型获得的，这些细胞类型在DNA损伤反应、细胞周期进程、生长因子信号转导和细胞凋亡的调节中参与蛋白质的过表达或表达不足。这些发现最终可能有助于设计新的策略，以提高癌症治疗的治疗率。尽管影响放射敏感性的细胞功能的知识迅速发展，我们仍然不能解释大多数临床观察到的正常组织和肿瘤对放射治疗反应的异质性，我们也不能准确预测哪些个体肿瘤将被局部控制，哪些患者将在放射治疗后发生更严重的正常组织损伤。然而，缺失或功能丧失突变的几个候选基因可能与改变的细胞放射敏感性相关（例如，ATM、p53、BRCA2）。正常组织对辐射敏感性的一些差异可能是由于这些基因的效应较轻的突变、杂合性或多态性而发生的。最后，正在研究将遗传不稳定性、辐射敏感性和癌症易感性联系起来的分子机制。
We have provided an overview of recent studies that have greatly expanded our knowledge of the molecular and cellular mechanisms that determine the sensitivity or resistance to ionizing radiation. Much of this knowledge was obtained by studying tumor and nontumor cell types that under- or overexpress proteins involved in the regulation of the DNA damage response, cell cycle progression, growth factor signal transduction, and apoptosis. These findings may ultimately be useful in devising new strategies to improve the therapeutic ratio in cancer treatment. Despite the rapid advances in knowledge of cellular functions that affect radiosensitivity, we still cannot account for most of the clinically observed heterogeneity of normal tissue and tumor responses to radiotherapy; nor can we accurately predict which individual tumors will be locally controlled and which patients will develop more severe normal tissue damage after radiotherapy. However, several candidate genes for which deletion or loss of function mutations may be associated with altered cellular radiosensitivity (e.g., ATM, p53, BRCA2) have been identified. Some of the differences in normal tissue sensitivity to radiation may occur because of mutations with milder effects, heterozygosity, or polymorphisms of these genes. Finally, molecular mechanisms linking genetic instability, radiosensitivity, and predisposition to cancer are being examined.