The effect of folate analogues on the thymidine utilization by human and rat marrow cells and the effect on the deoxyuridine suppression test.

Abstract

Summary The deoxyuridine (dU) suppression test assesses the capacity of marrow cells or activated lymphocytes to convert exogenous dU into thymidine. In addition, the effect of the added cobalamin or folate on the result is used to determine the nature of the deficiency in megaloblastic marrows. This study shows that folates have a considerable effect on the uptake of labelled thymidine by marrows from patients with megaloblastic anaemia in the absence of added dU. Less thymidine was taken up by megaloblastic marrow cells if they were first incubated with 5-formyltetrahydrofolate, 10-formyltetrahydrofolate or tetrahydrofolate. 5-Methyltetrahydrofolate increased thymidine uptake in cobalamin-deficient marrows and reduced thymidine uptake in folate-deficient marrows. These results could be explained if added folates facilitated utilization of endogenous dU. However, the addition of folates or cobalamin did not affect the validity of a dU suppression test with human marrow. More marked changes were present on the addition of folates to rat marrow cells both from control and nitrous oxidetreated animals.