Fornace Albert J, Amundson Sally A, Do Khanh T, Meltzer Paul, Trent Jeffrey, Bittner Michael
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mil Med. 2002 Feb;167(2 Suppl):13-5.
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.
我们使用人髓系肿瘤细胞系（ML-1），检测到低至2 cGy的γ射线剂量可诱导几种应激反应基因的mRNA表达。例如，CIP1/WAF1和GADD45诱导的剂量反应在2至50 cGy范围内似乎呈线性，且没有诱导阈值的证据。尽管2 cGy和5 cGy的照射未导致ML-1细胞的克隆效率出现任何可检测到的降低，也未导致细胞凋亡增加，但这些照射确实产生了短暂的细胞周期延迟。我们还使用荧光cDNA微阵列杂交技术来研究低剂量γ射线照射后的转录应激反应，并鉴定其他辐射反应基因，以便纳入我们正在开发的应激特异性微阵列中。这些研究为生理相关剂量的分子反应提供了见解，而高剂量研究不一定能推断出这些反应。使用高通量阵列将能够鉴定多种应激反应基因，这些基因在多种细胞类型和组织中均可被辐射诱导。预期转录应激反应将为监测辐射暴露和检测个体差异提供一种分子方法。
