Studies on Synergism in Combinations of Anti-Tumour Agents in Chick Embryos

Experiments have been carried out in which the effects of hydroxyurea alone and 5-BUdR alone, as well as in combination, on the development of chicken embryos were studied. The results were as follows: 1. Pilot experiments showed that neither hydroxyurea (0.05 mg/egg) or BUdR (0.025 mg/ egg) alone produced abnormalities during development. 2. When hydroxyurea was administered at 24 hours incubation and 5-BUdR 6 hours later, mortality was high. Mortality decreased as the interval between the two treatments was lengthened to 12 hours and 24 hours. 3. The incidence of beak abnormalities and micromelia rose when hydroxyurea treatment was followed by 5-BUdR by 6 hours or 12 hours. The incidence and severity of the defects declined as the interval was increased to 24 hours. 4. Whether 5-BUdR was injected first followed by hydroxyurea or hydroxyurea was followed by 5-BUdR, when the interval between the initial and the second injection was 6 or 12 hours, the toxic effects and the typical symptoms observed in the embryos were similar. 5. When the time interval between the injection of 5-BUdR followed by hydroxyurea was 24 hours, the mortality as well as incidence of typical abnormalities were reduced considerably. 6. It is supposed that the absence of any remarkable morphological defects when embryos were treated either with hydroxyurea or BUdR alone might be due to a repair mechanism in the DNA of the cells. The pronounced synergistic effects of combination of hydroxyurea and 5-BUdR reported here, could be due to the blockade of thede-novo biosynthesis of DNA.