| Research Abstract |
Immune deficient mice are useful as host of human tumor xenografts (HTXS), especially nude mouse has been widely used in evaluation of new antitumor drugs. We and many others have shown that the nude mouse/IITX model has possessed closed clinical reproducibility as an antitumor drug evaluation system. The SCID mouse (scid/scid) is a potential new recipient of HTX, and it has been reported that the mouse has advantages in the establishment of certain types of human tumor when compared with the nude mouse. In addition, recent gene engineering technology has led to mice with similar phenotype, but different mechanisms, to SCID mouse such as the recombination activating gene-2 (RAG-2) knockout mouse. In this study, we compared toxicity of mice to antitumor agents and sensitivities of HTXs in SCID mice with those in nude mice in order to validate the use of the SCID mouse in this field.
In toxicity study, SCID mouse showed rather hyper toxic sensitivities to topoisomerase II inhibitors and DNA intercalaters although RAG-2 knockout mouse showed no different sensitivities.
Sensitivities to antitumor drugs of HTXs implanted in C.B-17-scid and in BALB/cA-nu were compared. In a total of 2,5 pairs of corresponding experiments with each host mouse strain (5 HTXS x 5 drug treatment groups), we obtained consistent results in 23 (92.0%) experiments consisting of 10 which were both significantly effective and 13 which were both ineffective, although the remainir2g two (8.0%) experiments showed inconsistent results. A human T-cell lymphoma cell line, LM-2-JCK, implanted in nude mice, was resistant to treatment with 65 mg/kg of cyclaphasphamide. However, this tumor showed sensitive to the same treatment when implanted in either SCID mice or mice with a recombination activating gene-2 defect [BALB/cA-TgH(RAG-2)], suggesting that the genetic immune background of the host mouse should not be overlooked as a factor affecting tumors.
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