Suzuki Keiji, Kodama Seiji, Watanabe Masami
Division of Radiation Biology, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
Yakugaku Zasshi. 2006 Oct;126(10):859-67. doi: 10.1248/yakushi.126.859.
Accumulated evidence has shown that exposure to low-dose radiation, especially doses less than 0.1 Gy, induces observable effects on mammalian cells. However, the underlying molecular mechanisms have not yet been clarified. Recently, it has been shown that low-dose radiation stimulates growth factor receptor, which results in a sequential activation of the mitogen-activated protein kinase pathway. In addition to the activation of the membrane-bound pathways, it is becoming evident that nuclear pathways are also activated by low-dose radiation. Ionizing radiation has detrimental effects on chromatin structure, since radiation-induced DNA double-strand breaks result in discontinuity of nucleosomes. Recently, it has been shown that ATM protein, the product of the ATM gene mutated in ataxia-telangiectasia, recognizes alteration in the chromatin structure, and it is activated through intermolecular autophosphorylation at serine 1981. Using antibodies against phosphorylated ATM, we found that the activated and phosphorylated ATM protein is detected as discrete foci in the nucleus between doses of 10 mGy and 1 Gy. Interestingly, the size of the foci induced by low-dose radiation was equivalent to the foci induced by high-dose radiation. These results indicate that the initial signal is amplified through foci growth, and cells evolve a system by which they can respond to a small number of DNA double-strand breaks. From these results, it can be concluded that low-dose radiation is sensed both in the membrane and in the nucleus, and activation of multiple signal transduction pathways could be involved in manifestations of low-dose effects.
越来越多的证据表明，暴露于低剂量辐射，尤其是小于0.1 Gy的剂量，会对哺乳动物细胞产生可观察到的影响。然而，其潜在的分子机制尚未阐明。最近的研究表明，低剂量辐射会刺激生长因子受体，从而导致丝裂原活化蛋白激酶途径的一系列激活。除了膜结合途径的激活外，低剂量辐射也会激活核途径这一点也变得越来越明显。电离辐射对染色质结构有有害影响，因为辐射诱导的DNA双链断裂会导致核小体的连续性中断。最近的研究表明，共济失调毛细血管扩张症中发生突变的ATM基因的产物ATM蛋白，能够识别染色质结构的改变，并通过在丝氨酸1981处的分子间自磷酸化而被激活。使用抗磷酸化ATM的抗体，我们发现在10 mGy至1 Gy的剂量范围内，活化的和磷酸化的ATM蛋白在细胞核中被检测为离散的焦点。有趣的是，低剂量辐射诱导的焦点大小与高剂量辐射诱导的焦点大小相当。这些结果表明，初始信号通过焦点生长而放大，并且细胞进化出一种能够对少量DNA双链断裂做出反应的系统。从这些结果可以得出结论，低剂量辐射在细胞膜和细胞核中都能被感知，并且多种信号转导途径的激活可能参与低剂量效应的表现。
