Characterization of conditions in which dipyridamole enhances methotrexate toxicity in L1210 cells.

In vitro studies in exponentially growing L1210 cells utilizing DNA flow cytometry and cell proliferation measurements indicate enhancement of methotrexate effects by Dipyridamole provided: Methotrexate concentrations exceed those required to shut off maximally de novo pathways of purine and pyrimidine synthesis (i.e. 30 nM for 48 h), and Dipyridamole concentrations exceed 3 microM. In 10% fetal calf serum, this concentration inhibits tritiated thymidine uptake by about 80%. These data should prove helpful in the planning of clinical studies with dipyridamole or other inhibitors of nucleoside transport used to potentiate inhibitors of de novo pathways.