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Studies on genetic and microbiologicail quality of human tumor xenografts lines as a tool for animal experiments

作为动物实验工具的人类肿瘤异种移植物系的遗传和微生物质量研究

基本信息

批准号：
05454690
负责人：
OHNISHI Yasuyuki
金额：
$ 3.52万
依托单位：
Central Institute for Experimental Animals
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

Background : Human tumor xenografts (HTXs) are a useful tool for animal experiments especially for evaluation of new antitumor drugs. We have been establishing HTXs, and have developed tumor chemosensitivity panels for new drug evaluation using them.Purpose : With regard to quality control (problems in chanes into mouse type tumors and/or artificial cross-contamination among tumor lines), we studied genetic profiling, and effects of long-term passaging on tumor properties such as growth and chemosensitivities, and we discuss the use of cryopreservation stock of HTXs and periodic replacement in order to maintain reproducibility of the experimental results. Methods : We examined isozyme markers and DNA fingerprinting to identify species and individuality of the tumors, respectively. Growth curves and sensitivities to antitumor drugs were examined using HTXs with different passaging in nude mice. Results : Among the tumors we maintained, five human tumors were found to have changed to mouse origin from their isozyme markers and were excluded. We identified the individuality of tumors which we used for the chemosensitivity panels by DNA fingerprinting, and their properties were stable for long-term passaging in nude mice. However, growth speed and chemosensitivities to drugs were altered with long-term passaging, although DNA fingerprint analysis did not show any obvious changes with passaging. Conclusions : Genetic profiling, such as isozyme markers and DNA fingerprinting, is useful for identify individuality of experimental HTXs, and tumors should be renewed periodically even when there are no signs of artificial contamination when they are used in experiments which require continuous reproducibility of experimental results.

背景：人类肿瘤异种移植物（HTX）是一种非常有用的动物实验工具，尤其是用于评价新的抗肿瘤药物。我们一直在建立HTX，并开发了用于新药评估的肿瘤化疗敏感性面板。目的：关于质量控制（转化为小鼠型肿瘤和/或肿瘤系间人为交叉污染的问题），我们研究了遗传谱，以及长期传代对肿瘤性质如生长和化学敏感性的影响，我们讨论了使用HTX的冷冻保存储备和定期更换，以保持实验结果的重现性。方法：采用同工酶标记和DNA指纹图谱技术对肿瘤进行种属鉴定和个体鉴别。用不同代次的HTX在裸鼠体内观察其生长曲线及对抗癌药物的敏感性。结果：在我们保留的肿瘤中，发现5个人肿瘤从其同工酶标记物改变为小鼠来源，并被排除。我们通过DNA指纹鉴定了用于化疗敏感性小组的肿瘤的个体性，并且它们的性质在裸鼠中长期传代是稳定的。然而，生长速度和药物敏感性的改变与长期传代，虽然DNA指纹分析没有显示任何明显的变化与传代。结论：基因谱分析，如同工酶标记和DNA指纹，是有用的，以确定实验HTX的个性，和肿瘤应定期更新，即使当没有人为污染的迹象时，它们被用于实验中，需要实验结果的连续再现性。