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Induced Ribotide Reductive Conversion Defect by Hydroxyurea and Its Relationship to Megaloblastosis¹

Department of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas 75235

During therapy with an antineoplastic agent, hydroxyurea, early abrupt megaloblastic changes were evident in the marrow. Correlative biochemical studies suggested that the megaloblastosis resulted from an abrupt decrease in reductive conversion of ribotide to deoxyribotide and that hydroxyurea induces defective reductive conversion. Evidence for similar changes in the spleen in considerably less, suggesting that splenic hematopoietic mesenchyme may have a DNA biosynthetic pathway that is different from that of the bone marrow.

¹ Supported by USPHS Grant No. CA 06853 from the National Cancer Institute.

Received 6/ 8/66. Accepted 1/11/67.