Published online by Cambridge University Press: 01 August 2014
The cytotoxic effects of hydroxyurea and of related hydroxamic acid derivatives in vivo are briefly described. They occur selectively in tissues with high rates of cell renewal and they are of brief duration. Tissue concentration of hydroxyurea diminish rapidly as the result of renal excretion and metabolism; there is a close temporal relation between the physiological disposition of the agents and the cytotoxic changes. Hydroxyurea induces an immediate inhibition of DNA synthesis in proliferating tisdsues such as thymus, small intestine, and regenerating liver. Autoradiographic studies of mouse duodenum using tritiated thymidine have shown that the lethal susceptibility to hydroxyurea is restricted to cells in the S-phase of the mitotic cycles. Cells in G1, G2, and M are not damaged by the agent.
The original work summarized briefly herein is being published in detail elsewhere. It has been supported in part by grants CA-03192 and CA-08748 from the National Cancer Institute, U. S. Public Health Service.