Deoxycytidine Pathway in Separated Normal and Leukemic Leukocytes With Effects of Cell Culture

Abstract

Abstract Enzymes of dC metabolism were studied in glass-column-separated normal and leukemic cells. Supernatants of sonicated cells were incubated with dC-3H or dCMP-3H and the end products separated with paper chromatography. Greatest recovery of dCTP, dUMP, and TTP occurred with myeloblasts and monoblasts. Mature granulocytes, and normal and leukemic lymphocytes gave the greatest breakdown to uracil. Myelocytes and lymphoblasts gave intermediate results. Leukemic lymphocytes from different patients varied greatly in their end products, but most did show evidence of TMP synthetase activity contrary to previous reports. Recovery of products of TMP synthetase and, to a lesser extent, dCMP deaminase and dC kinase activities was greatest in cells having or developing a potential for mitosis. CLL-L whose extracts showed appreciable production of dCTP, dUMP, and TdR compounds, however, did not regularly produce blast cells in response to PHA in culture. Cellular extracts of N-L, or CLL-L from cases which responded to PHA did show, on the other hand, a considerable increase in accumulation of these compounds from initial low values during culture.