Analyses of effects of heavy ion irradiation on expression of viral and cellular genes

我们利用重离子照射细胞并接种病毒，分析了HIV-1、HBV、HCV等病毒的感染机制。作为重离子，He， C或Ne被使用，作为对照，用紫外线或x射线/γ射线照射，或用各种化合物处理。辐照靶细胞采用人细胞系C8166和NP-2/CD4/CCR5（转染CD4和CCR5基因的NP2细胞）、hbv阳性的Alexander细胞系或HCV复制子阳性的Huh-7细胞系。这些细胞用重离子照射，然后感染HIV-1。辐照细胞中逆转录病毒DNA的数量增加。较高剂量的辐照没有引起这种增加。HIV-1在细胞上的吸附量没有明显增加。这些结果表明，相对低剂量的重离子照射细胞会促进HIV-1病毒粒子的掺入或逆转录以及病毒RNA的转录。以重离子或x射线照射c8166ce后，更多携带HTLV-I的细胞NFκB表达增强，而HTLV-I Tax的表达不受辐射影响。在HBV阳性细胞中，重离子辐照倾向于增强HBV抗原的产生。在HCV复制子阳性的Huh-7细胞中，重离子辐照对HCV复制子的数量没有明显影响。在重离子照射细胞中，CD133 mRNA和NFκB mRNA的表达增强，而组蛋白去乙酰化酶（HDAC）、Ku80和多聚adp核糖聚合酶的mRNA表达降低。对辐照细胞对病毒感染的敏感性分析表明，重离子辐照对病毒感染有特异性影响，而紫外线或x射线辐照对病毒感染没有特异性影响。重离子辐照和x射线辐照在生物效应上的差别一般被认为仅仅表现在它们的相对生物效应（RBE）上。我们的研究表明，重离子辐照与x射线或紫外线有质的区别。少

We have analyzed the infection mechanism of viruses, such as HIV-1, HBV or HCV, using cells irradiated with heavy ions and inoculated with them. As heavy ions, He, C or Ne was used and as controls, irradiation with UV or X-ray/γ ray, or treatment with various chemical compounds was used. As target cells for irradiation, the human cell lines C8166 and NP-2/CD4/CCR5 (NP2 cells transduced with CD4 and CCR5 genes), HBV-positive Alexander cell line or HCV replicon-positive Huh-7 line was used.The cells were irradiated with heavy ions and then infected with HIV-1. The amount of reverse transcribed viral DNA was increased in the irradiated cells. Irradiation with higher doses did not induce this increase. The amount of HIV-1 adsorbed to the cells did not increase significantly. These results suggest that irradiation of cells with relatively low doses of heavy ions will promote incorporation of HIV-1 virions or reverse transcription as well as transcription of viral RNA.Irradiation of C8166 ce … More lls harboring HTLV-I with heavy ions or X-ray enhanced expression of NFκB, whereas expression of HTLV-I Tax was not affected by the irradiation. In HBV-positive cells, heavy ion irradiation tended to enhance the production of HBV antigens. In HCV replicon-positive Huh-7 cells, heavy ion irradiation did not apparently affect the number of HCV replicon.In cells irradiated with heavy ions, expression of CD133 mRNA or NFκB mRNA was enhanced, whereas mRNA for histon deacetylase (HDAC), Ku80 or poly-ADP ribose polymerase was decreased.Analyses of susceptibilities of irradiated cells to virus infection showed the specific effects exerted by irradiation with heavy ions, but not by irradiation with UV or X-ray. The difference in biological effects between heavy ion irradiation and X-ray irradiation has generally been considered to be present merely in their relative biological effects (RBE). Our study suggested that there is a qualitical difference between irradion with heavy ions and X-ray or UV. Less