Inhibition of glycoprotein and glycolipid synthesis in hamster embryo cells by cytosine arabinoside and hydroxyurea

Abstract

THE nucleoside, 1-β-D-arabinofuranosylcytosine (ara-C) and the unrelated compound, hydroxyurea, are known to inhibit DNA replication in bacterial and animal cells^1–3. Arabinofuranosyl cytidine-5′-triphosphate (ara-CTP) specifically interferes with the action of DNA polymerase II in bacterial cell extracts⁴, whereas hydroxyurea affects the ribonucleoside diphosphate reductase reaction⁵. We have shown that ara-C and hydroxyurea bring about transformation of hamster embryo cells in tissue culture⁶. Further, it has also been demonstrated that ara-C inhibits the incorporation of ³H-D-glucosamine (a precursor of N-acetyl-neuraminic acid) into glycoproteins and glycolipids of hamster embryo fibroblasts and transformed cells⁷. In continuing these experiments we have been interested in, first, determining the site or sites of action of ara-C (presumably as its triphosphate) in the cell and second, studying other inhibitors of DNA replication as to their possible effect on glycoprotein and glycolipid synthesis.