Changes in the Deoxyribonucleoside Triphosphate Pools of Mouse 5178Y Lymphoma Cells following Exposure to Methotrexate or 5-Fluorouracil1

SUMMARY Changes are reported in the deoxyribonucleoside triphos-phate pools of L5178Y cells during their exposure to methotrexate or 5-fluorouracil. For both drugs the intracell-ular deoxythymidine triphosphate level fell rapidly, accom panied by an increase in deoxycytidine triphosphate concen tration. These changes were associated with increases in the levels of deoxyadenosine triphosphate and deoxyguanosine triphosphate, which were marginal in methotrexate-containing cultures but considerable in cultures containing 5-fluo rouracil. The possible significance of these events is dis cussed in relation to the presently accepted mechanisms responsible for the cytotoxicity of methotrexate and 5-fluo rouracil.