免疫缺陷动物筛选人转移癌中动物非期望死亡原因分析

目的:阐明免疫缺陷动物筛选人转移癌组织过程中主要的非正常死亡原因,为人类肿瘤动物模型建立和筛选提供借鉴.方法:采用皮下、原位、肾包膜下移植等多种方法对267只BALB/c裸小鼠接种(或注射)人肾细胞癌、前列腺癌临床标本、DU-145细胞系,分析成瘤率、肝脏病变情况(临床表现、病理切片、死亡时间分布)等.结果:移植肾细胞癌标本的总成瘤率为21.7%(35/161),转移率为1.2%(2/161).移植前列腺癌临床标本均未成瘤或发生转移;移植DU-145细胞系成瘤率为100%(20/20),转移率为25%(5/20).肾细胞癌临床标本移植小鼠肝脏病变率为58.4%(94/161),前列腺癌临床标本移植小鼠肝脏病变率为43.4%(46/106),DU-145细胞系移植小鼠无1例肝脏病变发生.移植肾细胞癌、前列腺癌标本肝脏病变小鼠死亡高峰与小鼠总体死亡高峰趋势一致,均发生在每年的冬春季.结论:肝脏病变是造成动物非正常死亡的主要原因,严格控制SPF环境方可保证肿瘤动物模型的顺利建立.

Unexpected death analysis of immune-deficient mice when they were used for establishing human metastatic cancer models

Objective:To elucidate the major reasons for unexpected death nude mice when they were used for establishing human metastatic cancer models. Methods: The fresh specimens of human renal cell carcinoma (RCC), prostate cancer (PC), and DU-145 cells were transplanted / injected into nude mice ecotopically and orthotopically. Tumorigenesis and pathological changes (including the symptoms, pathological sections, survival time, etc.) of mouse liver were investigated subsequently. Results: The tumorigenesis and metastasis rates were respectively 21.7% (35/161) and 1.2% (2/161) after implantation of RCC sample, and were respectively 100% (20/20) and 25% (5/20) after implantation of DU-145 cell line, while there was no tumorigenesis or metastasis after implantation of PC specimens. Liver pathological changes were found in 58.4% (94/161) of mice implanted with RCC samples and in 43.4% (46/106) of mice implanted with PC samples. No pathological lesion was found in mice implanted with DU-145 cells. The death peak of mice with pathological changes after implanting RCC and PC samples was consistent with that of the total mice used in this study, all occurring in the winter and spring of the year. Conclusion: The pathological changes of liver appear to be the major reason of unexpected death of the nude mice when they were used for establishing human metastatic cancer models. A specified pathogen-free environment is very important for establishment of the models.