Liu Chao, Lin Qun, Yun Zhong
a Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut 06520.
Radiat Res. 2015 May;183(5):487-96. doi: 10.1667/RR13959.1. Epub 2015 May 4.
Molecular oxygen has long been recognized as a powerful radiosensitizer that enhances the cell-killing efficiency of ionizing radiation. Radiosensitization by oxygen occurs at very low concentrations with the half-maximum radiosensitization at approximately 3 mmHg. However, robust hypoxia-induced signal transduction can be induced at <15 mmHg and can elicit a wide range of cellular responses that will affect therapy response as well as malignant progression. Great strides have been made, especially since the 1990s, toward identification and characterization of the oxygen-regulated molecular pathways that affect tumor response to ionizing radiation. In this review, we will discuss the current advances in our understanding of oxygen-dependent molecular modification and cellular signal transduction and their impact on tumor response to therapy. We will specifically address mechanistic distinctions between radiobiological hypoxia (0-3 mmHg) and pathological hypoxia (3-15 mmHg). We also propose a paradigm that hypoxia increases radioresistance by maintaining the cancer stem cell phenotype.
长期以来，分子氧一直被认为是一种强大的放射增敏剂，可提高电离辐射的细胞杀伤效率。氧的放射增敏作用在极低浓度下即可发生，半最大放射增敏作用时的氧浓度约为3 mmHg。然而，在氧分压<15 mmHg时可诱导强烈的缺氧诱导信号转导，并可引发广泛的细胞反应，这些反应会影响治疗反应以及恶性进展。特别是自20世纪90年代以来，在识别和表征影响肿瘤对电离辐射反应的氧调节分子途径方面取得了巨大进展。在这篇综述中，我们将讨论目前在理解氧依赖性分子修饰和细胞信号转导及其对肿瘤治疗反应的影响方面取得的进展。我们将具体探讨放射生物学缺氧（0 - 3 mmHg）和病理性缺氧（3 - 15 mmHg）之间的机制差异。我们还提出了一种模式，即缺氧通过维持癌症干细胞表型来增加放射抗性。
