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Differential Effects of Hydroxyurea on Survival of Proliferating Cells in Vivo¹

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and Fels Research Institute, Temple University Medical School, Philadelphia, Pennsylvania 19140

A single injection of hydroxyurea inhibits DNA synthesis in continuously dividing cells (crypt cells of the small intestine, germinal centers of lymph follicles, basal layer of the tongue epithelium) and in quiescent tissues that are stimulated to synthesize DNA and divide by an appropriate stimulus (regenerating liver after partial hepatectomy, folic acid-stimulated kidney, isoproterenol-stimulated salivary gland). However, whereas a single injection of hydroxyurea produces extensive necrosis in the DNA-synthesizing cells of continuously dividing tissues, the same dose is ineffective in producing necrosis in the DNA-synthesizing cells of stimulated tissues. This differential action of hydroxyurea seems therefore capable of distinguishing DNA-synthesizing cells from different types of tissues.

¹ Supported by research grants from the Life Insurance Medical Research Fund and the USPHS (AM-05590 from the National Institute for Arthritis and Metabolic Disease, GM-10269 from the National Institute of General Medical Science, DE-02678 from the National Institute of Dental Research, and CA-07174 from the National Cancer Institute).

Received 6/ 4/68. Accepted 9/21/68.