X-射线诱导大肠癌细胞PCD与p53转录表达改变

　　探讨大肠癌HT-29、Lovo细胞在X-射线诱导PCD过程中不同类型p53基因转录表达改变，为肿瘤的放射治疗方案提供新的理论线索。方法　选择几种临床常用X-射线放射治疗剂量诱导大肠癌细胞呈现PCD特征，应用免疫细胞化学和细胞原位杂交技术对含有不同类型p53基因的HT-29、Lovo两种大肠癌细胞p53蛋白表达和p53 mRNA转录进行对比分析。结果　两种细胞经X-射线照射后均表现出较为典型的细胞凋亡改变，两种细胞p53 mRNA转录均有所增强。HT-29细胞p53蛋白表达增强，Lovo细胞p53蛋白却始终不能检出。结论　p53基因确实参与了X-射线诱导大肠癌细胞的PCD过程。但是，突变型和野生型p53基因的转录表达改变不尽相同，提示不同类型p53基因发挥的作用不同。

VARIATION OF p53 GENE TRANSCRIPTION AND EXPRESSION IN COLO-RECTAL CARCINOMA CELL PCD INDUCED BY X-RAY

JI Dai-jin　CAO Yan

　　Department of Gastroenterology， No.452 Hospital of PLA， Chengdu 610061，China

　　Abstract：Objective　To investIGAte the variations of p53 gene transcription and expression in colo-rectal carcinoma HT-29 and Lovo cells lines during the programmed cell death (PCD) induced by X-ray and to search for the new clues for radiation treatment of carcinoma. Methods　Several conventional doses of X-ray (5 Gy， 10 Gy， 15 Gy， 20 Gy， 25 Gy) were chosen in this study. After the PCD was induced by the doses， the comparative analysis were conducted in HT-29， Lovo cell lines that have different types of p53 genes by immunohistochemical and in situ hybridization. ResulTS　After X-ray irradiation the cells showed typical characteristics of PCD. Both the cells increased p53 mRNA transcriptions. p53 protein expression was increased in HT-29 but no p53 protein was found in Lovo. Conclusion　The results show that p53 protein actually participated in the PCD induced by X-ray. In this process， however， the changes are different between the wild and mutant p53 genes. It suggests that different p53 genes play different roles in the process.

　　Key words：　Gene，p53；　Radiobiology;　PCD；　Tumor cells，cultured

　　许多研究发现，治疗肿瘤的多种措施可能诱导肿瘤细胞产生程序化死亡(Programmed Cell Death， PCD)。各种DNA损伤因子对细胞的损伤作用亦可通过诱导细胞PCD而发挥作用。在此过程中，p53基因可与多种细胞生长因子、癌基因等相互调节参与诱导细胞PCD。文献报告［1，2］，X-射线介导的细胞毒作用可能与依赖p53基因的PCD有关。但该过程中p53基因mRNA和蛋白发生怎样的改变却知之甚少。为此，作者用X-射线诱导大肠癌细胞呈现PCD，应用免疫组化(Immunohistochemistry，IHC)和原位杂交(In situ Hybridization，ISH)技术对含有不同类型p53基因的HT-29、Lovo细胞中p53 mRNA和蛋白表达改变进行了比较研究，现报告如下。