Targeted and nontargeted effects of low-dose ionizing radiation on delayed genomic instability in human cells
Targeted and nontargeted effects of low-dose ionizing radiation on delayed genomic instability in human cells
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DOI：
10.1158/0008-5472.can-06-3697
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发表时间：
2007-02-01
期刊：
影响因子：
11.2
通讯作者：
Morgan, William F.
中科院分区：
文献类型：
--
作者：
Huang, Lei;Kim, Perry M.;Morgan, William F.
所有人都会受到一定程度的辐射照射，低剂量辐射诱发癌症的风险是基于剂量与后续效应之间存在线性非阈值关系的假设。因此，风险可以从高辐射剂量线性外推到非常低的剂量。然而，适应性反应、旁观者效应和死亡诱导效应可能影响与低剂量辐射照射有关的健康效应。适应性反应是一种现象，通过这种现象，受到亚致死辐射剂量照射的细胞对随后的高剂量辐射照射变得不那么敏感。旁观者效应是在未辐照但与辐照细胞接触或接受辐照细胞可溶性信号的细胞中观察到的非靶向效应。这些未被击中的旁观者细胞可以表现出通常与直接辐射暴露相关的损伤。死亡诱导效应是一种现象，即来自显示辐射诱导的染色体不稳定性的人-仓鼠杂交细胞的培养基对未受辐射的亲本细胞具有毒性。在这项研究中，我们表明，人RKO细胞不表现出适应性反应，旁观者效应，或死亡诱导效应，细胞杀伤，或延迟基因组不稳定性在一个稳定转染质粒为基础的绿色荧光蛋白测定测量同源重组和延迟突变/缺失事件。然而，由一些染色体不稳定的RKO衍生物调节的生长培养基诱导基因组不稳定性，表明这些细胞可以分泌引起未照射细胞反应的因子。此外，低辐射剂量抑制诱导延迟基因组不稳定性的后续高剂量，辐射诱导的基因组不稳定性的适应性反应的指示。这些结果突出了固有的。这可能会导致细胞对低剂量辐射照射的反应的变异性，并增加了与评估这些低剂量的潜在危害有关的不确定性。
All humans receive some radiation exposure and the risk for radiation-induced cancer at low doses is based on the assumption that there is a linear non-threshold relationship between dose and subsequent effect. Consequently, risk is extrapolated linearly from high radiation doses to very low doses. However, adaptive responses, bystander effects, and death-inducing effect may influence health effects associated with low-dose radiation exposure. Adaptive response is the phenomenon by which cells irradiated with a sublethal radiation dose can become less susceptible to subsequent high-dose radiation exposure. Bystander effects are nontargeted effects observed in cells that were not irradiated but were either in contact with or received soluble signals from irradiated cells. These non-hit bystander cells can exhibit damage typically associated with direct radiation exposure. Death-inducing effect is a phenomenon whereby medium from human-hamster hybrid cells displaying radiation-induced chromosomal instability is toxic to unirradiated parental cells. In this study, we show that human RKO cells do not exhibit adaptive response, bystander effect, or death-inducing effect, as measured by cell killing, or delayed genomic instability in a stably transfected plasmid-based green fluorescent protein assay measuring homologous recombination and delayed mutation/deletion events. However, growth medium conditioned by some chromosomally unstable RKO derivatives induced genomic instability, indicating that these cells can secrete factor(s) that elicit responses in nonirradiated cells. Furthermore, low radiation doses suppressed the induction of delayed genomic instability by a subsequent high dose, indicative of an adaptive response for radiation-induced genomic instability. These results highlight the inherent. variability in cellular responses to low-dose radiation exposure and add to the uncertainties associated with evaluating potential hazards at these low doses.