Characterisation of a Murine Renal Cell Carcinoma Model Potentially Useful in Selecting New Chemotherapeutic Agents

Abstract

A murine renal cell carcinoma transplantable in CDF1 mice, the RC tumour was characterised and used for the evaluation of chemotherapeutic agents. Survival time as well as tumour growth were consistent and reproducible. Median survival time (MST) of mice inoculated intraperitoneally with 106 tumour cells was 16.6 days and 21.4 days after subcutaneous transplant. The percent increase in lifespan (ILS) and long-term survivors (LTS) on Day 60 were used to assess the effectiveness of the drugs. Sixteen drugs with known clinical activity and 4 new drugs were evaluated. Three different doses per drug were given intraperitoneally on Days 1, 5, 9, 13 and 17 (schedule q4D x 5). The most effective agents against the RC tumour were cyclophosphamide (ILS > 387%; LTS = 100%), methyl-CCNU (ILS > 209%; LTS = 50%) and cisplatin (ILS > 200%; LTS = 60%). A new epoxide derivative: the triglycidyl urazole (TGU) showed a high effectiveness (ILS > 185%; LTS = 90%). Methotrexate, bleomycin, 5-fluorouracil, vindesine and vinblastine revealed a satisfactory activity (ILS > 50%). In these experiments, the RC tumour revealed as responsive to alkylating agents and antimetabolites as P388 leukaemia and almost as responsive to antimitotics as L1210 leukaemia. These results would suggest that the RC tumour is more sensitive to chemotherapeutic agents than P388 and L1210 leukaemias and may be used in selecting new anticancer drugs in a primary screen.