The Effect of Hydroxyurea on Differentiated Marrow Erythroid Precursors ∗

Abstract

Summary

A single i.v. dose of hydroxyurea (0.9 g/kg) produced transient marrow erythroid depopulation and reticulocytopenia in the mouse. Within minutes after drug administration there was a virtually complete erradication of marrow DNA synthesis which persisted for approximately 2 hr. Erythroid cell cycle kinetics, estimated with colchicine, revealed an entry of erythroid cells into mitosis for 80 min followed by no further accumulation of metaphase forms until the seventh hour. Thereafter erythroid cells accumulated in mitosis at a normal rate. These findings are consistent with the hypothesis that hydroxyurea kills erythroid cells in DNA synthesis; the initial 80-min accumulation of erythroid mitoses represents the progression of G2 cells into mitosis. Unaffected cells in G1 at the time of drug administration require 7-8 hr to progress through DNA synthesis, G2, and enter mitosis. From these data it would appear that hydroxyurea may prove a useful agent in the study of erythropoiesis because of its selective effect on DNA synthesis in the erythroid series.