Effect of thymidine on the survival of mice with EL4 tumors.

The effect of thymidine (dlhd) on the growth of EL4 thymoma tumors in syngeneic C57BL/6 mice was determined. In vitro, EL4 cells are approximately 10-fold more sensitive to dlhd than are many other tumor lines, and they are 100-fold more sensitive than are normal cells; dThd (2.5 to 5 @g/ml)were cytostatic, and dlhd (12.5 to 25 pg/mI) cytotoxic to EL4 cells. The half-life of dlhd in mouse serum was approximately 60 mm, so that 20-g mice given injections with 24 mg dlhd at 4hr intervals during the day and with 30 mg dlhd before an 8-hr interval overnight were estimated to maintain systemic concen trations of dlhd greater than 25 @.tg/g. Groups of 10 mice were given 2.2 x 1o@or 2.4 x 1O@EL4 cells i.p. and then treated with 0.86% NaCI or dlhd on the 4and 8-hr regimen. The mean death times of the NaCIand dlhd-treated mice were 9.9 or 16.4 days and 17.7 or 23.1 days, respectively. The 7-day differences between the death times of NaCIand dlhd-treated mice were significant to p < 0.0001 , and the 7-day delay in death time was equivalent to that expected from a 3-bogreduc tion in viable EL4 cells. The mean death time of 10 NaCI treated mice given 2 x 102 cells was 23.9 days, and the death time for 7 of 10 dlhd-treated mice was 31 .4 days. Three dlhd treated mice given 2 x 102 cells survived until sacrificed at 60 days. The data show that although some sensitive cells may escape inhibition and replicate under the injection regimen used, dlhd is cytotoxic to sensitive EL4 cells in vivo. The data suggest that dThd might be a useful chemotherapeutic agent for tumors that have the same level of sensitivity as EL4.