PRACTICAL ROLE OF GENETIC PROFILING AND PRESERVATION STOCK OF HUMAN TUMOR XENOGRAFT LINES AS A TOOL IN ANIMAL-EXPERIMENTS FOR ANTITUMOR DRUG-EVALUATION

Human tumour xenografts (HTXs) are a useful tool for animal experiment s especially for evaluation of new antitumour drugs. We have been esta blishing HTXs, and have developed tumour chemosensitivity panels for n ew drug evaluation using them. With regard to quality control (problem s in changes into mouse-type tumours and/or artificial cross-contamina tion among tumour lines), we studied genetic profiling, and effects of long-term passaging on tumour properties such as growth and chemosens itivities, and we discuss the use of cryopreservation stock of HTXs an d periodic replacement in order to maintain reproducibility of the exp erimental results. We examined isozyme markers and DNA fingerprinting to identify species and individuality of the tumours, respectively. Gr owth curves and sensitivities to antitumour drugs were examined using HTXs with different passaging in nude mice.Among the tumours we mainta ined, five human tumours were found to have changed to mouse origin fr om their isozyme markers and were excluded. We identified the individu ality of tumours which we used for the chemosensitivity panels by DNA fingerprinting, and their properties were stable for long-term passagi ng in nude mice. However, growth speed and chemosensitivities to drugs were altered with long-term passaging, although DNA fingerprint analy sis did not show any obvious changes with passaging. Genetic profiling , such as isozyme markers and DNA fingerprinting, is useful to identif y individuality of experimental HTXs, and tumours should be renewed pe riodically even when there are no signs of artificial contamination wh en they are used in experiments which require continuous reproducibili ty of experimental results.