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On the Curability of Experimental Neoplasms

I. A-Methopterin and Mouse Leukemias^*

( Kettering-Meyer Laboratory [Affiliated woth Sloan-Kettering Institute], Southern Research Institute, Birmingham, Ala.)

1. A correlation between the number of leukemic cells (L4946 and L1210) inoculated into mice and "curability" with A-methopterin under very favorable conditions has been observed.

2. Bioassays of tissues of mice inoculated with L4946 leukemic cells showed that such cells when placed in the peritoneal cavity rapidly reached the blood and other tissues. If the leukemic cell inoculum was low, A-methopterin repressed the growth of leukemic cells in the spleen, lymph nodes, and liver, even though the latter was apparently a site of storage of folic acid metabolites.

3. On the assumption that the correlation between the size of inoculum and "curability" of L4946 leukemia with A-methopterin is related to the mutation rate of the leukemic population to A-methopterin resistance, efforts have been made to calculate the mutation rate and the generation time of such leukemic cells and to test certain hypotheses regarding experimental chemotherapy with A-methopterin. Various theoretical considerations have been presented on the basis of these calculations.

^* This work was supported by a grant-in-aid from the American Cancer Society.

Received 4/24/57.