Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), School of Medicine, Bethesda, MD 20814, USA.
DNA Repair (Amst). 2012 Jan 2;11(1):12-21. doi: 10.1016/j.dnarep.2011.10.024. Epub 2011 Nov 23.
A founding concept of radiobiology that deals with X-rays, γ-rays and ultraviolet light is that radiation indiscriminately damages cellular macromolecules. Mounting experimental evidence does not fit into this theoretical framework. Whereas DNA lesion-yields in cells exposed to a given dose and type of radiation appear to be fixed, protein lesion-yields are highly variable. Extremely radiation resistant bacteria such as Deinococcus radiodurans have evolved extraordinarily efficient antioxidant chemical defenses which specifically protect proteins and the functions they catalyze. In diverse prokaryotes, the lethal effects of radiation appear to be governed by oxidative protein damage, which inactivates enzymes including those needed to repair and replicate DNA. These findings offer fresh insight into the molecular mechanisms of radiation resistance and present themselves as new opportunities to study and control oxidative stress in eukaryotes, including mammalian cells and their cancer cell counterparts.
放射生物学的一个基本概念是,X 射线、γ 射线和紫外线会无差别地损伤细胞大分子。越来越多的实验证据却不符合这一理论框架。虽然在受到特定剂量和类型辐射的细胞中,DNA 损伤的产生似乎是固定的,但蛋白质损伤的产生则具有高度的可变性。极度耐辐射的细菌,如 Deinococcus radiodurans,已经进化出非常有效的抗氧化化学防御机制,专门保护蛋白质及其催化的功能。在不同的原核生物中,辐射的致死效应似乎是由氧化蛋白质损伤所控制的,这种损伤会使包括修复和复制 DNA 所需的酶在内的酶失活。这些发现为辐射抗性的分子机制提供了新的见解,并为研究和控制真核生物(包括哺乳动物细胞及其癌细胞对应物)中的氧化应激提供了新的机会。