Rescue of human lymphoid cells from the effects of methotrexate in vitro.

In protection experiments (5-formyltetrahydrofolate or 5-methyltetrahydrofolate added to cultures in vitro at the same time as methotrexate), 5-methyltetrahydrofolate af forded the same degree of protection as did formyltetrahydrofolate for phytohemagglutinin-stimulated peripheral blood lymphocytes and for methotrexate-resistant (R) and methotrexate-sensitive (S) sublines of CCRF-CEM. Either reduced folate at 100 /¿Mprotected phytohemagglutininstimulated lymphocytes or CCRF-CEM-S against 1 ¿¿M methotrexate almost completely, against 10 f*M metho trexate partially, but not against 100 /IM methotrexate. For CCRF-CEM-R 100 /KMreduced folate partially protected against 10 ¿¿M methotrexate but did not protect against 100 ¡it» methotrexate. In rescue experiments, cells were exposed in vitro to methotrexate for a 1-hr period, washed, and then resuspended in conditioned medium containing the rescue agent. Again 5-methyltetrahydrofolate equalled 5-formyl tetrahydrofolate in efficacy. Either reduced folate at 5 /¿M rescued phytohemagglutinin-stimulated lymphocytes or CCRF-CEM-S from 50 juMmethotrexate, and 500 pu con centrations of either agent rescued CCRF-CEM-S from 500 PLUmethotrexate, CCRF-CEM-R is not rescued from 500 /¿Mmethotrexate (1 hr) by 500 /¿Magent. The in vivo rescue of cells after high-dose methotrexate administration is more adequately modeled in vitro by rescue experiments than by protection experiments.