Radiation induced non-targeted response: mechanism and potential clinical implications.
Radiation induced non-targeted response: mechanism and potential clinical implications.
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辐射引起的非靶向反应：机制和潜在的临床意义。
DOI：
10.2174/1874467211104020096
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发表时间：
2011-06
影响因子：
2.7
通讯作者：
Ivanov VN
中科院分区：
文献类型：
--
作者：
Hei TK;Zhou H;Chai Y;Ponnaiya B;Ivanov VN
几代辐射生物学的学生都被教导说，遗传的生物效应需要对DNA的直接损伤。辐射诱导的非靶向/旁观者效应代表了我们对电离辐射的放射生物学效应的认识的一种范式转变，因为细胞核和细胞外效应也可能促成低剂量辐射照射的生物后果。虽然辐射诱导的旁观者效应已经在各种生物系统中得到了很好的证明，包括3D人体组织样本和整个生物体，但其机制尚不清楚。最近的研究表明，直接照射后，细胞内NF-κ B依赖性基因白细胞介素8、白细胞介素6、环氧合酶2、肿瘤坏死因子和白细胞介素33表达增加，产生具有自分泌/旁分泌功能的细胞因子和前列腺素E2，进一步激活信号通路，诱导旁观者细胞NF-κ B依赖性基因表达。遗传性DNA改变可以在辐射暴露后传播到细胞许多代，并且旁观者细胞以类似于直接击中细胞的方式表现出基因组不稳定性，这一观察结果表明，低剂量辐射反应是各种调节因子的复杂相互作用。讨论了辐射诱发的继发性癌症的非靶向反应的潜在意义。更好地了解非靶向效应的机制将是非常宝贵的，以评估其临床相关性和如何可以操纵旁观者现象，以增加治疗增益的放射治疗。
Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced non-targeted/bystander effects represent a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety of biological systems, including 3D human tissue samples and whole organisms, the mechanism is not known. There is recent evidence that the NF-κB-dependent gene expression of interleukin 8, interleukin 6, cyclooxygenase-2, tumor necrosis factor and interleukin 33 in directly irradiated cells produced the cytokines and prostaglandin E2 with autocrine/paracrine functions, which further activated signaling pathways and induced NF-κB-dependent gene expression in bystander cells. The observations that heritable DNA alterations can be propagated to cells many generations after radiation exposure and that bystander cells exhibit genomic instability in ways similar to directly hit cells indicate that the low dose radiation response is a complex interplay of various modulating factors. The potential implication of the non-targeted response in radiation induced secondary cancer is discussed. A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy.