5-fluorodeoxyuridine decreases the effect of arabinofuranosyl-cytosine in undifferentiated human B lymphocytes.

Abstract

An activated lymphocyte population was isolated from tonsils of 3-6 years old children by density gradient centrifugation. The isolated light density (LD) cells were bearing early B lymphocyte markers and were 5-6 times more active in DNA synthesis than the high density (HD) lymphocytes. It was found that about 70% of CdR was deaminated and converted into dTMP. The cells were very sensitive to araC, but the incorporation of [14C] CdR was twice more sensitive to araC than that of [5-3H]CdR. This effect can be explained by the interconversion of araC into araT nucleotide via the CdR interconversion pathway. This suggestion was also supported by the effect of 5-F-UdR, which decreased the inhibition of DNA synthesis caused by araC. 5-FUdR the inhibitor of thymidylate synthase, possibly decreases the interconversion of araC into araTTP, and its action via a smaller dTTP pool of the cells. Our data suggest, that the sensitivity of cells to araC may depend on the capacity of the CdR----TdR interconversion pathway, which, however, changes during the normal differentiation process of lymphocytes. Thus, the sensitivity of different malignant cells to araC is determined by the differentiation stage at which they were arrested during cell transformation.