Sokolov Mykyta, Neumann Ronald
Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Int J Mol Sci. 2015 Dec 31;17(1):55. doi: 10.3390/ijms17010055.
Exposure to ionizing radiation (IR) is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD) rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR) compared to those observed after a short-term high-dose IR exposure (HDIR). With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes.
在现实生活中,人类不可避免地会接触到电离辐射(IR);IR的危害主要源于其致突变、致癌和细胞杀伤能力。几十年来,人们对人类细胞对低剂量/低剂量率(LD)IR的反应进行了广泛研究。这些研究表明,与短期高剂量IR暴露(HDIR)后观察到的情况相比,低剂量IR(LDIR)后的分子、细胞和组织水平反应有所不同。随着20世纪90年代末高通量技术的出现,如DNA微阵列,人们还发现LDIR后基因表达的变化普遍存在。已证明只有非常有限的一部分基因会被LDIR持续上调,包括CDKN1A。对IR在人类细胞中诱导的生物学效应和机制的进一步研究表明,LDIR激活的分子和细胞过程,包括转录改变,通常与保护反应有关,有时还与兴奋效应有关。LDIR后观察到了一些不同的反应,包括旁观者效应和适应性反应。人们发现,不仅mRNA水平,而且miRNA水平的基因表达变化对于这些效应至关重要,这对辐射防护目的具有重要意义。