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目的:通过动物体内试验研究EB病毒(EBV)对人正常细胞的致瘤性,并检测我国正常人群对EBV的易感性,试图建立EBV诱发人淋巴细胞肿瘤模型。方法:在严重联合免疫缺陷动物即SCID小鼠体内移植健康成人外周血淋巴细胞(PBL),每鼠腹腔接种1×108个PBL。对接种VCA/IgA阴性献血员PBL的动物,移植后1周内经腹腔注射B95-8标准株EBV悬液作为实验感染,而接种VCA/IgA阳性献血员PBL的动物不再进行实验感染。结果:在接受12名健康成人PBL移植并感染EBV的19只SCID小鼠中,肿瘤诱发率分别为91.7%(11/12名)和84.2%(16/19只鼠)。诱发瘤常见于小鼠腹腔后壁和纵隔,具有侵袭性和致死性,患瘤小鼠平均存活时间65.5天。EBV诱发瘤是结节状实体瘤,显微镜下观察肿瘤细胞呈大裂—无裂混合细胞。组织病理学和免疫病理学研究表明,肿瘤类型是人源B细胞性恶性淋巴瘤。诱发瘤原位分子杂交显示肿瘤细胞核内存在EB病毒小核酸分子EBER-1和人类基因组Alu序列。电子显微镜观察肿瘤细胞核内存在EB病毒颗粒。肿瘤细胞表达EB病毒BZLF1蛋白阳性。结论:SCID/人淋巴细胞嵌合体是研究EBV感染和致瘤性的敏感动物模型,且获得了EBV引起人类正常细胞在体内发生肿瘤的直接依据。因而证实了EBV对人类细胞的致瘤作用,进一步明确机体免疫缺陷因素在肿瘤发生中起重要作?
OBJECTIVE: To study the tumorigenicity of Epstein-Barr virus (EBV) on human normal cells in vivo and to test the susceptibility to EBV in normal population in China and to establish EBV-induced human lymphocyte tumor model. Methods: Healthy adult peripheral blood lymphocytes (PBLs) were transplanted in SCID mice with severe combined immunodeficiency. Each mouse was inoculated intraperitoneally with 1 × 108 PBLs. Animals vaccinated with PBL of VCA / IgA negative donors were infected intraperitoneally with EBV suspension of B95-8 within 1 week after transplantation, while animals vaccinated with PBL of VCA / IgA positive donors were no longer infected experimentally. Results: The tumor induction rates were 91.7% (11/12) and 84.2% (16/19 mice) in 19 SCID mice receiving 12 healthy adult PBLs and infecting EBV respectively. Induced tumor common in mice abdominal wall and mediastinal peritoneal, with invasive and lethal, the average survival time of tumor-bearing mice 65.5 days. EBV-induced tumors are nodular solid tumors, the tumor cells were observed under a microscope split - no split cells. Histopathological and immunopathological studies have shown that the tumor type is human B-cell malignant lymphoma. Induced neoplasms in situ hybridization showed the presence of Epstein-Barr virus nucleic acid molecule EBER-1 and human genome Alu sequences in tumor nuclei. Electron microscopy observed the presence of EBV particles in the nucleus of tumor cells. Tumor cells express Epstein-Barr virus BZLF1 protein positive. CONCLUSIONS: SCID / human lymphocyte chimera is a sensitive animal model for EBV infection and tumorigenicity and a direct basis for the EBV-induced tumorigenesis in human normal cells. Thus confirming the tumorigenic effect of EBV on human cells, to further clarify the role of immunodeficiency in vivo plays an important role in tumorigenesis?