Sokolov M V, Smirnova N A, Camerini-Otero R D, Neumann R D, Panyutin I G
Department of Nuclear Medicine, Clinical Center, NIH, Bldg. 10 Room 4D45, 9000 Rockville Pike, Bethesda, MD 20892, United States.
Gene. 2006 Nov 1;382:47-56. doi: 10.1016/j.gene.2006.06.008. Epub 2006 Jun 27.
Exposure of cells to ionizing radiation (IR) produces changes in the expression level of a large number of genes. However, less is known of gene-expression changes caused by local radiation exposure from radionuclides within cells. We studied changes in the genome-wide gene expression induced by decay of 125I incorporated into DNA as [125I]-iododeoxyuridine (125I-IUdR) in normal IMR-90 human lung fibroblasts and compared them with the changes produced by external gamma-radiation delivered at high (HDR) or low (LDR) dose rate. We found that more than 2000 genes were consistently up- or down-regulated following HDR and LDR gamma-radiation. The profiles of differentially expressed genes following HDR and LDR shared about 64% (up) and 74% (down) genes in common, with many genes identified as radiation-responsive for the first time. In contrast, in all only 206 genes changed their expression level in the 125I-IUdR-treated cells, even though the total number of DNA double-strand breaks (DSB) produced by 125I-IUdR exceeded that produced by the gamma-radiation. With few exceptions, the expression levels of 125I-IUdR-responsive genes were also altered following gamma-irradiation. Therefore, nuclear DNA-localized decays of 125I produce 10 times fewer differentially expressed genes than whole-cell exposure to gamma-radiation of comparable dose. These results suggest that the effect of IR on the changes in global gene expression depends on the distribution of energy depositions within the cell. In contrast to cell survival, DNA DSB may not be the major factor modulating changes in gene expression following irradiation.
细胞暴露于电离辐射（IR）会导致大量基因的表达水平发生变化。然而，对于细胞内放射性核素局部辐射暴露引起的基因表达变化了解较少。我们研究了正常IMR - 90人肺成纤维细胞中作为[125I] - 碘脱氧尿苷（125I - IUdR）掺入DNA的125I衰变诱导的全基因组基因表达变化，并将其与高剂量率（HDR）或低剂量率（LDR）外部γ辐射产生的变化进行比较。我们发现，HDR和LDR γ辐射后有2000多个基因持续上调或下调。HDR和LDR后差异表达基因的谱图共有约64%（上调）和74%（下调）的基因相同，许多基因是首次被鉴定为辐射反应性基因。相比之下，在125I - IUdR处理的细胞中，尽管125I - IUdR产生的DNA双链断裂（DSB）总数超过了γ辐射产生的数量，但只有206个基因改变了表达水平。除了少数例外，γ辐射后125I - IUdR反应性基因的表达水平也发生了改变。因此，125I的核DNA定位衰变产生的差异表达基因比全细胞暴露于同等剂量的γ辐射少10倍。这些结果表明，IR对全局基因表达变化的影响取决于细胞内能量沉积的分布。与细胞存活情况不同，DNA DSB可能不是调节辐射后基因表达变化的主要因素。
