[Effect of rescue treatment with high doses of methotrexate (MTX) followed by leucovorin (LV) on neoplastic cells (HeLa line) and normal sensitized peripheral lymphocytes].

Employing the pharmacologic simulator under time lapse microcinematography described elsewhere, the authors study in this work the rescue treatment with high doses of methotrexate (MTX) followed by leucovorin rescue 6 and 24 hours after MTX addition. The experiments were done on mixed cultures of HeLa cells and HeLa cell-sensitized human lymphoblasts. MTX alone produces an extensive cell degeneration, that is never complete, 2300 micrograms/ml leucovorin have no toxic effect neither upon HeLa cells nor lymphoblasts. Higher amounts of leucovorin stimulate the growth of the neoplastic cells, but the lymphoblasts are not affected. Leucovorin added 6 or 24 hours after MTX inhibits the mitotic activity completely for 54 to 62 hours. Neoplastic cells death rate is never higher than 20 per 100. Lymphoblasts die much earlier reaching 50 per 100 after 50-58 hours. Cell degeneration is accompanied by large morphological and morphodynamic modifications. Rescue treatment in vitro, under condition simulating in vivo kinetics of the drugs is not able to eliminate the cancer cells. Actually, leucovorin stimulates the growth of the neoplastic cells and rescues great part of them out from the G0 state into the active cell cycle when leucovorin is added 6 or 24 hours after MTX administration, no growth stimulus is observed and the rescue effect is not produced; in the case of the lymphoblasts this is due to the fact that highest toxic of MTX on them takes place during the second elimination phase of the drug.