The influence of deoxycytidine monophosphate (dCMP) on the cytotoxicity of hydroxyurea in the embryonic spinal cord of the mouse.
On day 10 of pregnancy NMRI mice received an intraperitoneal injection of either 500 mg/kg hydroxyurea (HU) or 500 mg/kg HU plus 500, 700, 800, or 900 mg/kg deoxycytidine monophosphate (dCMP). Three hours after application of the substances, the animals received 5 microCi/g 3H-thymidine i.p. One hour later the animals were sacrificed and the embryos were removed. Autoradiographs of the embryos served to determine the percentage of necroses, labelled necroses, mitoses, labelled mitoses, and labelled neuroepithelial cells of the spinal cord. Optimal inhibition of HU effects was achieved by application of 700 mg/kg dCMP. The cytotoxic effects of HU on neuroepithelial cells could be partially but not completely inhibited by simultaneous application of dCMP. The duration of HU-induced DNA synthesis inhibition was shortened after simultaneous dCMP application. A strong increase of the labelling index and shortening of the G2-phase duration of neuroepithelial cells after simultaneous application of HU and dCMP was striking as compared to the results obtained from untreated or HU-treated animals.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D003843:Deoxycytidine Monophosphate / Q000494:pharmacology*; D003845:Deoxycytosine Nucleotides / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006918:Hydroxyurea / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008940:Mitotic Index; D009336:Necrosis; D011247:Pregnancy; D013116:Spinal Cord / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology
D003845:Deoxycytosine Nucleotides; D003843:Deoxycytidine Monophosphate; D006918:Hydroxyurea