The use of dihydrofolate reductase in studies of mixed populations of sensitive and resistant leukemic cells.

Mathematical models are presented which attempt to relate the interplay between such factors as life span of a leukemic animal, how early drug treatment is initiated, the survival of sensitive and resistant leukemic cells in treated animals, the incidence of mutation from the sensitive state to the resistant state, and the dihydrofolate reductase levels in mixed populations of sensitive and resistant cells. A computer was used to generate theoretical mixed populations of resistant and sensitive leukemic cells during three simulated passages in drug-treated animals. This was done so as to mimic the actual enzyme data collected during the development of an amethopterin-resistant subline. It is concluded that dihydrofoÃ-atereducÃ-asecan be used as a meaningful bio chemical marker in studies of emerging antifolate-resistant leukemic cells.