Leucovorin antagonizes the effects of trimetrexate on mouse hemopoietic progenitors.

Trimetrexate (2, 4, diamino -5- methyl - 6 [3, 4, 5, trimethoxyanilino) methyl] quinazoline) (TMQ) is a non-classic folate antagonist that is used as an antineoplastic and antipneumocystis agent with promising results. TMQ and methotrexate (MTX) toxicities are comparable. Leucovorin (N-5-formyltetrahydrofolate) (LV) is used to prevent the toxic effects of MTX. In this study the effects of LV on TMQ induced hemopoietic progenitor damage are studied in a murine model. Changes of pluripotent stem cells (colony forming units spleen, CFU-S), granulocyte-macrophage committed progenitors (GM-CFC), erythroid committed progenitor (BFU-E) levels in the bone marrow were followed after administration to mice of a single dose of TMQ or of simultaneous injection of TMQ and LV. Results show that the latter significantly reduces the effects of the former on peripheral blood cells and on hemopoietic progenitors.