p73变异体研究现状及其在肿瘤放疗中的应用前景

p73基因是p53抑癌基因家族的新成员。 p73有两组蛋白异构体: TAp73和DNp73。 TAp73具有诱导细胞周期停滞和细胞凋亡的能力, 而DNp73却有与之相反的能力, 具有肿瘤促进作用。 对p73基因两面性的特点及研究进展作一综述。 最后结合重离子治疗肿瘤, 探讨了p73联合重离子治疗的新思路。 p73 was the first identified homologue of the tumor suppressor gene, p53. p73 has two groups of protein isoforms: TAp73 and DNp73. TAp73 can induce cell cycle arrest, resulting in the ability of apoptosis, however DNp73 has antagonistic property of a tumor promoting effect. In this paper, the dual roles of p73 gene and its research progress was reviewed. Finally, combined with heavy ion treatment of tumor, we explored some new ideas of p73 heavy ion joint therapy.     

重离子对人胃癌细胞DNA错配修复基因MSH2 表达的影响

采用高传能线密度(LET) 重离子辐照人胃癌SGC7901 细胞,应用流式细胞技术、蛋白质印迹法(Western blot) 及反转录聚合酶链式反应(RT-PCR) 观察重离子诱导人胃癌SGC7901 细胞周期、凋亡和MSH2 表达状况。结果表明: 与对照组相比,SGC7901 细胞在辐射后72 h G2/M 期所占细胞比率(33.26±0.08) 和凋亡率(24.16±0.64) 均达到峰值,且呈时间依赖性增加;经重离子照射后,DNA错配修复基因MSH2 mRNA 和蛋白表达水平在6 h 最高。结果提示:重离子在体外诱导SGC7901 细胞周期阻滞和凋亡,且具有显著的时间依赖性效应;重离子在一定剂量和时间下,诱导了SGC7901 细胞MSH2 基因表达。DNA错配修复基因MSH2 可能参与了重离子辐照诱导胃癌细胞DNA损伤的修复应答。Human gastric cancer cell SGC7901 were irradiated with high linear energy transfer (LET) carbon ion. Apoptotic cells after irradiation were analyzed by flow cytometry and expression of MSH2 genes in the irradiated cells was detected by western blot and RT-PCR assay. Compared with the control group, we found that the number of G2/M (33.26±0.08) or apoptosis (24.16±0.64) of SGC7901 cells reached a maximum after irradiation at 72 h in a dose dependent manner. And heavy ion irradiation efficiently up-regulated the expression of MSH2 gene at 4.0 Gy after being irradiated 6 h. These results imply that heavy ion beam could induce cell apoptosis and cell cycle arrest in time-dependent manners. Furthermore, expression of MSH2 genes activated by carbon ion irradiation suggests that DNA mismatch repair gene MSH2 might be involved in DNA repair pathways.     

集簇性DNA损伤在辐射研究中的进展

高LET重离子引起的集簇性DNA损伤会造成细胞突变、 癌变和凋亡。 促进肿瘤细胞凋亡一直是治愈肿瘤的出发点, 所以集簇性DNA损伤已经成为放射生物学领域研究的热点问题。 由于其提取和检测方法多样, 但并没有一个详细和完整的方案对集簇性DNA损伤进行透彻分析。 综述了集簇性DNA损伤的特点和详细讨论了集簇性DNA损伤最新研究进展, 简介了集簇性DNA损伤的研究方法, 以期为集簇性DNA损伤在放疗中的研究提供一些参考。 Clustered DNA damage which caused by high LET heavy ion radiation can lead to mutation, tumorigenesis and apoptosis. Promoting apoptosis of cancer cells is always the basis of cancer treatment. Clustered DNA damage has been the hot topic in radiobiology. The detect method is diversity, but there is not a detail and complete protocol to analyze clustered DNA damage. In order to provide reference for clustered DNA damage in the radiotherapy study, the clustered DNA damage characteristics, the latest progresses on clustered DNA damage and the detecting methods are reviewed and discussed in deteil in this paper.     

姜黄素对重离子辐射损伤小鼠睾丸组织的防护作用研究

探讨姜黄素(Curcumin,简称Cur)对重离子辐射损伤小鼠睾丸组织的防护作用。小鼠灌胃不同剂量的Cur后给予4 Gy剂量~(12)C~(6+)离子束全身单次照射。24 h后对小鼠睾丸组织形态学变化进行观察,并测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和过氧化氢酶(CAT)活性。结果显示:中、高浓度Cur预处理组对小鼠睾丸组织的形态具有较好的保护作用;低、中浓度Cur预处理组MDA含量显著降低(P0.05);与单纯照射组相比,低浓度Cur预处理组SOD活性水平和中浓度Cur预处理组CA了活性水平显著提高(P0.05)。结果表明:Cur对重离子全身辐射小鼠的抗氧化系统有一定的激活效应,对辐射损伤有一定的防护作用,其机制可能与Cur清除自由基,保护脂质和蛋白质有关。