75mGyX射线诱导小鼠胸腺细胞转录因子CREB、NF—kB及AP1水平变化

Alteration in transcription factor binding in murine thymocytes after low dose radiation

目的：为了解低剂量x射线全身照射对小鼠胸腺细胞基因转录调控的影响。方法：采用凝胶电泳迁移率变化分析和寡核苷酸竞争抑制方法检测低剂量x射线对小鼠胸腺细胞基因转录调控的影响。结果：迁移率变化证实75mGyX射线全身照射小鼠后4h，胸腺细胞核蛋白提取物的转录因子CREB及NF-kB与其基因启动部位增强子控制序列的结合活性分别增强6倍及4．3倍，AP1增强2倍。竞争抑制试验证实CREB及NF-kB与其控制序列特异地结合。结论：低剂量X射线全身照射选择性地激活胸腺细胞CREB、NF-kB及AP1，通过与增强子控制序列位点的结合．特异地诱导基因转录。

Objective: To study the effect of low dose radiation on gene transcription regulation of murine thymocytes. Methods: Alteration in transcription factor binding in murine thymocytes 4 h after whole body irradiation (WBI) with 75 mGy X-rays was investigated with gel mobility shift assay. Results:Increased binding to CREB,NF-kB and API consensus sequences was found with nuclear extracts prepared from thymocytes of irradiated versus sham-irradiated mice. Binding to the CREB,NF-kB and API consensus sequences by nuclear extracts derived from irradiated mice was 6-fold, 4, 3-fold and 2-fold higher than that from sham-irradiated respectively. The present report demonstrates that WBI with 75 mGy X-rays is capable of increasing expression of CREB,NF-kB and API in murine thymocytes. Competition with the cold olignucleotide containing the consensus sequences for CREB and NF-kB resulted in loss of the shifted band, indicating specific binding. Conclusion:X-ray activation of select transcription factors,which bind certatin consensus sites in prometers,may cause specific induction of gene transcription.