Stress-gene induction by low-dose gamma irradiation.
Stress-gene induction by low-dose gamma irradiation.
复制标题
低剂量伽马射线照射诱导应激基因。
DOI：
10.1093/milmed/167.suppl_1.13
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发表时间：
2002
影响因子：
1.2
通讯作者：
M. Bittner
中科院分区：
文献类型：
--
作者：
A. Fornace;S. Amundson;K. Do;P. Meltzer;J. Trent;M. Bittner
使用人骨髓肿瘤细胞系 (ML-1)，我们检测到低至 2 cGy 剂量的伽马射线对几种应激反应基因 mRNA 表达的诱导。例如，诱导 CIP1/WAF1 和 GADD45 的剂量反应在 2 至 50 cGy 范围内似乎呈线性，并且没有显示诱导阈值的证据。尽管 2 和 5 cGy 暴露不会导致任何可检测到的克隆效率降低，也不会导致 ML-1 细胞凋亡增加，但这些暴露确实产生了短暂的细胞周期延迟。我们还使用荧光 cDNA 微阵列杂交来研究低剂量伽马射线后的转录应激反应，并确定其他辐射反应基因以包含在我们正在开发的应激特异性微阵列中。这些研究提供了对生理相关剂量的分子反应的深入了解，这不一定可以从高剂量研究中推断出来。高通量阵列的使用将允许鉴定多种细胞类型和组织中可辐射诱导的多种应激反应基因。期望转录应激反应将提供一种分子方法来监测辐射暴露和检测个体间差异。
Using a human myeloid tumor cell line (ML-1), we detected induction of mRNA expression of several stress-responsive genes by doses of gamma rays as low as 2 cGy. For instance, the dose response for induction of CIP1/WAF1 and GADD45 appears to be linear over the range of 2 to 50 cGy and shows no evidence of a threshold for induction. Although 2 and 5 cGy exposures did not result in any detectable reduction in cloning efficiency nor in increased apoptosis in ML-1 cells, these exposures did produce a brief cell-cycle delay. We also used fluorescent cDNA microarray hybridization to investigate transcriptional stress responses following low doses of gamma rays and to identify additional radiation-responsive genes for inclusion in a stress-specific microarray we are developing. These studies provide insight into the molecular responses to physiologically relevant doses, which cannot necessarily be extrapolated from high-dose studies. The use of high throughput arrays will allow the identification of multiple stress-responsive genes that are radiation inducible in a variety of cell types and tissues. The expectation is that transcriptional stress responses will provide a molecular approach to monitoring for radiation exposure and detecting interindividual differences.