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裸鼠因胸腺先天发育不良、T细胞免疫功能缺损而成为移植异种肿瘤的理想动物模型。然而,裸鼠c型RNA病毒有被移植瘤活化的可能,国外已发现了几十例。从1981年起,我们对10余株长期传代的裸鼠移植瘤模型进行了比较系统的电镜检测,先后在大鼠BERH-2肝癌移植瘤(RL-1)、人肺鳞癌移植瘤(LSX-83)以及人肝癌移植瘤(LTNM_4)三株裸鼠模型中检出c型RNA病毒,进而对它们的活化,侵染机理进行了探讨,现报告如下。一般认为,裸鼠内源性c型RNA病毒在活化初期仅在包围移植瘤的基质中显现,而后2—3代,才侵染进入移植瘤的结缔组织、瘤细胞的间隙及其胞浆内。我们在RL-1中所见基本与之相符,但c型病毒的侵染范围似更大——瘤细胞的核周隙萌生芽孢以及毛细血管腔出现病毒颗粒,以往未见有报道。LTNM_4株的瘤细胞质膜上病毒芽孢多见,但胞浆内却查无病毒颗粒;LSX-83株从40代起,连续l5代c型病毒仅局限于瘤细胞的间隙。上述种种,提示裸鼠c型RNA病毒活化侵染过程的复杂性。 c型RNA病毒对移植瘤的侵染导致移植瘤生物学特性的改变。RL-1被侵染后,瘤细胞的间隙和内质网小池出现异常致密的有形物质;移植瘤生长缓慢;瘤组织回种大鼠皮下不能成活,而传代早期能生长。对LSX-83的侵染影响表现为移植瘤呈分化升级的趋向;瘤细胞核仁出现典型的核仁微分离。LTNM_4株的主要改变是暗细胞消失;线粒体内嵴有较多囊泡。长期传代的裸鼠异种移植瘤,其形态学特征会出现某些变化,但较c型病毒的侵染影响则小得多。内源性,c型病毒的基因组通常整合于宿主的染色体中,其潘化、侵染的机理同前尚不太清楚。订人认为,功能性肿瘤产生的蛋白质类活性物质可能对c型病毒有较强的诱导作用。RL-1与LTNM。株均乃高AFP含量的移植肝癌,c型病毒的激活可能与AFP有夫。至于淆化的e型病毒较长时期滞留在LSX-83瘤细咆的间隙,推测LSX-83瘤细胞表面可能缺乏c型病毒受体抑或具有某种抵御机制。三株裸鼠异种侈植瘤中查见c型病毒均在连续传代40代后。对于长期传代裸鼠肿瘤模型的病毒检测是鉴定模型质量的必要手段。
Nude mice due to congenital hypothyroidism, T cell immune dysfunction and become the ideal animal model of xenograft tumors. However, the nude mouse c-type RNA virus has the possibility of activation of transplanted tumors, dozens of cases have been found abroad. Since 1981, more than 10 long-term passaged nude mice xenograft models were systematically examined by electron microscopy. They were performed in rat RL-1 and RLX-1 tumor-bearing lung xenografts (LSX) -83) and human hepatocellular carcinoma xenografts (LTNM_4) were detected in three nude mouse models of c-type RNA viruses, and their activation, invasion mechanism were discussed are as follows. It is generally believed that the nude mouse endogenous c-type RNA virus in the initial activation of the only surrounded by transplanted tumor in the matrix showed, and then 2-3 generations, only infiltrated into the xenograft tumor, interstitial tumor cells and its cytoplasm . What we see in RL-1 is basically the same, but the scope of infection with c-type viruses seems to be even greater - there are no reports of cytoplasmic sporulation of tumor cells and virus particles in the capillary cavity. LTNM_4 strains of the tumor cell plasma membrane more common on the plasma membrane, but the cytoplasm was checked virus-free particles; LSX-83 strain from 40 onwards, for successive l5 generation c virus is confined to the tumor cell gap. All of the above suggest the complexity of activating infection process of nude mouse type C RNA virus. Infection of xenografts with c RNA virus results in the alteration of the biological characteristics of xenografts. RL-1 was infected, tumor cell gap and endoplasmic reticulum cell abnormal dense tangible material; tumor growth slow; tumor tissue subcutaneous rats can not survive, and early passage of growth. The infection of LSX-83 showed the tendency of xenograft tumors to differentiate and upgrade, and typical nucleoli separation occurred in nucleoli of tumor cells. The major change of LTNM_4 strain was that the dark cells disappeared; there were more vesicles in the inner mitochondria. Long-term passage of nude mice xenografts, the morphological characteristics of some changes, but the impact of c-virus infection is much smaller. Endogenous, c virus genome is usually integrated in the host chromosome, the pan, the mechanism of infection is not clear with the previous. Bookers believe that functional tumors of protein-type active substances may have a stronger c-type virus induction. RL-1 and LTNM. Strain are high AFP levels of transplanted liver cancer, c-type virus activation may be related to AFP husband. As confused e-type virus in the longer period of stay in the LSX-83 tumor cell roar gap speculated that LSX-83 tumor cell surface may lack of type C virus receptor or have some resistance mechanism. Three nude mice xenografts were found in c virus were continuous passage after 40 generations. For long-term transmission of tumor models in nude mice virus detection is necessary to identify the quality of the model.