Cell cycle phase specificity of hydroxyurea and its effects on the cell kinetics in embryonic spinal cord

Pregnant mice (NMRI) received an intravenous injection of 500 mg/kg of hydroxyurea (HU) on day 10 of gestation. The animals were killed 1, 1.5, 2, 2.5, 4, 6, 8 or 10 h after application of the drug and the embryos removed. Forty-five min. prior to sacrifice, the animals were given an intraperitoneal injection of 5 microCi/g 3H-thymidine (specific activity 5 Ci/mmol). From autoradiographs of the embryos the percentage of mitoses, necroses and labelled cells of the spinal cord was determined at the various time intervals. It was observed that HU inhibited DNA-synthesis in all S-phase cells for more than 4 hours. All cells damaged by HU did not start DNA-synthesis again and became necrotic. Only cells entering the S-phase after the influence of HU could replicate their DNA in a normal manner. It is assumed that HU possibly blocks cells in the G2-phase and in the mitosis for a certain period of time.