Abstract
Recent studies on the activity of antifolates have been directed at the perturbations in folate pools caused by inhibitors of dihydrofolate reductase. For the most part these studies have been restricted to the effects of methotrexate, but the effects of trimetrexate have also been examined. A constant feature of these results is the elevation of dihydrofolate which accompanies inhibition by both these agents (1–7). A variable result is the extent to which the reduced folate coenzymes are depleted following exposure to the antifolates. In several cell lines the reduction in tetrahydrofolate is quite modest (less than 40%) with the 10-formyltetrahydrofolate being maintained (1–5). In other cases such as L1210 cells in vivo there is a marked depletion of the reduced folate coenzyme pools (6). Preliminary studies with a rodent hepatoma cell line indicated that the reduced folate coenzymes are depleted by 80% or greater and this is compensated for by an increase in H2PteGlun and 10-HCO-H2PteGlun (7). The current study extends these investigations to the effect of methotrexate on the folate coenzymes in human HEPG2 hepatoma cells in vitro.
Published Version
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