Practical role of genetic profiling and preservation stock of human tumour xenograft lines as a tool in animal experiments for antitumour drug evaluation.
Human tumour xenografts (HTXs) are a useful tool for animal experiments especially for evaluation of new antitumour drugs. We have been establishing HTXs, and have developed tumour chemosensitivity panels for new drug evaluation using them. With regard to quality control (problems in changes into mouse-type tumours and/or artificial cross-contamination among tumour lines), we studied genetic profiling, and effects of long-term passaging on tumour 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. We examined isozyme markers and DNA fingerprinting to identify species and individuality of the tumours, respectively. Growth curves and sensitivities to antitumour drugs were examined using HTXs with different passaging in nude mice. Among the tumours we maintained, five human tumours were found to have changed to mouse origin from their isozyme markers and were excluded. We identified the individuality of tumours 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. Genetic profiling, such as isozyme markers and DNA fingerprinting, is useful to identify individuality of experimental HTXs, and tumours 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.
Ohnishi
Y
Y
Central Institute for Experimental Animals, Kawasaki, Japan.
Yamamoto
N
N
Ebukuro
M
M
Yoshimura
M
M
Sawa
N
N
Ueyama
Y
Y
Nomura
T
T
Katoh
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D015925:Cryopreservation; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000378:metabolism; D004341:Drug Evaluation; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D014021:Tissue Preservation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015415:Biomarkers; D004273:DNA, Neoplasm; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D005956:Glucose-6-Phosphate Isomerase