Investigation of the effect of hydroxyurea on the cell cycle and the development of necrosis in the embryonic CNS of mice

Abstract

On day 10 of gestation pregnant mice (strain NMRI) were given an intravenous injection of 500 mg/kg Hydroxyurea (HU). Simultaneously either 5 μCi/g or 10 μCi/g ³H‐thymidine (³H‐Tdr; specific activity 5 Ci/mmol) was administered to the animals. At various times after treatment embryos were removed, sectioned and prepared for autoradiography, light microscopy and electron microscopy. Two hours after administration of HU condensations of the chromatin structure could be detected electron microscopically in some cells. Thirty minutes later the nucleolus became smaller and denser, the cytoplasm shrank, and the cell organelles moved closer together. Three hours after application of the drug break‐down of the involved cells set in. As in the autora‐diograms about 98% of the counted necroses were labelled, and since labelled thymidine is almost exclusively incorporated during the S‐phase, it can be stated that HU influences only metabolic processes which take place during the S‐phase. From the morphological findings it can be concluded that in the case of the S‐phase‐specific metabolic pathway, which is influenced by HU, we are primarily dealing with DNA synthesis.