Cytidine Deaminase in Human Lymphocytes

PERIPHERAL blood lymphocytes in culture undergo cell division in the presence of the mitogenic stimulant phyto-haemagglutinin (PHA)1. Some of the metabolic processes that occur shortly after stimulation include phosphorylation of membrane bound phosphatidyl inositol2, acetylation of histones3, changes in cyclic GMP levels4, a pronounced elevation of uridine kinase activity5 and increases in RNA synthesis6 and protein synthesis7. These events are followed by the initiation of DNA replication within approximately 24 h8,9. Frequently, labelled uridine and thymidine are used as nucleic acid precursors to measure RNA and DNA biosynthesis. In one of these studies, Lucas observed that additions of cytidine inhibited the incorporation of labelled uridine into RNA in PHA-stimulated lymphocytes5. This finding was confirmed in this laboratory and these studies were expanded to include the effects of other nucleosides such as guanosine on lymphocytes from healthy donors and from patients with chronic lymphocytic leukaemia (CLL)10.