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

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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.