Low-dose Radiation Effects and Intracellular Signaling Pathways
Accumulated evidence has shown that exposure to low-dose radiation, especially doses less than 0.1 Gy, induces observable eŠects on mammalian cells. However, the underlying molecular mechanisms have not yet been clariˆed. 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
... ent that nuclear pathways are also activated by low-dose radiation. Ionizing radiation has detrimental eŠects 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 ampliˆed through foci growth, and cells evolve a system by which they can respond to a small number of DNA doublestrand 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 eŠects.