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Inhibition of RNA synthesis, a possible mode of the embryotoxic action of hydroxyurea

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Summary

14C-u-glucose and 32P-phosphate were given intravenously to pregnant rats, treated and untreated with hydroxyurea (HU). The incorporation of radio-activity into a variety of cell components of the embryo was measured. With this double-labelling technique it is possible to survey the effects of embryotoxic drugs on various pathways in mammalian embryos in vivo. Onset, extent and duration of the metabolic changes were measured after application of “non-teratogenic” and teratogenic doses of hydroxyurea (HU). 3 hrs after application of hydroxyurea only DNA synthesis is affected, whereas after 5 hrs RNA synthesis is also inhibited.

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References

  • Bochert, G., Krowke, R.: Effect of 5-fluoro-deoxycytidine (FCdr) on DNA metabolism of mouse embryos (CF 1). Teratology 8, 216 (1973)

    Google Scholar 

  • Bochert, G., Mewes, P., Krowke, R.: Labelling of RNA and DNA moieties of mammalian embryos in vivo by 14C-u-glucose and 32P-orthophosphate. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, 413–428 (1973)

    Google Scholar 

  • Burk, K. Y., Woods, M., Hunter, Y.: On the significance of glycolysis for cancer growth, with special reference to Morris rat hepatomas. J. nat. Cancer Inst. 38, 839–863 (1967)

    Google Scholar 

  • Burton, K.: A study of conditions and mechanism of the reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62, 315 (1956)

    Google Scholar 

  • Butcher, R. E., Scott, W. J., Kazmaier, K., Ritter, E. J.: Postnatal effects in rats of prenetal treatment with hydroxyurea. Teratology 7, 161–166 (1973)

    Google Scholar 

  • Chaube, S., Murphy, M. L.: The effects of hydroxyurea and related compounds on the rat fetus. Cancer Res. 20, 1448–1457 (1966)

    Google Scholar 

  • Chaube, S., Murphy, M. L.: Protective effect of deoxycytidilic acid (CdMP) on hydroxyurea—induced malformation in rats. Teratology 7, 79–88 (1973)

    Google Scholar 

  • Dobson, R. L., Cooper, M. F.: Incorporation of radioactivity from thymidine into mammalian glucose and glycogen. Biochim. biophys. Acta (Amst.) 254, 393–401 (1971)

    Google Scholar 

  • Köhler, E., Merker, H.-J., Ehmke, W., Wojnorowicz, F.: Growth kinetics of mammalian embroys during the stage of differentiation. Naunyn-Schmiedeberg's Arch. Pharmacol. 272, 169–181 (1972)

    Google Scholar 

  • Krowke, R.: Studies on the incorporation of 14C-glucose and 32P-phosphate into nucleic acids and other cell components of rat embryos in vivo. In: R. Bass, F. Beck, H.-J. Merker, D. Neubert, and B. Randhahn: Metabolic pathways in mammalian embryos during organogenesis and its modification by drugs. Berlin: Freie Universität 1970

    Google Scholar 

  • Krowke, R., Pielsticker, K., Siebert, G.: A simple fractionation procedure for studying incorporation of radioactively labelled precursors into mammalian main cell components. Naunyn-Schmiedegs Arch. Pharmak. 271, 121–124 (1971a)

    Google Scholar 

  • Krowke, R., Siebert, G., Neubert, D.: Biochemical screening test with 14C-glucose and 32P-phosphate for the evaluation of embryotoxic effects in vivo. Naunyn-Schmiedebergs Arch. Pharmak. 271, 274–288 (1971b)

    Google Scholar 

  • Krowke, R., Siebert, G., Neubert, D.: Effect of 5-fluoro-deoxycytidine, 5-fluorouracil and cycloheximide on the incorporation of 14C-glucose and 32P into different cell components of rat embryos in vivo. Naynyn-Schmiedebergs Arch. Pharmak. 268, 229–234 (1971c)

    Google Scholar 

  • Krowke R., Neubert D.: Embryonic intermediary metabolism under normal and pathologial conditions. In: Handbook of Teratology (J. G. Wilson, ed.) Sect. III; 6. New York: Academic Press, 1975 (in press)

    Google Scholar 

  • Morley, C. G. D., Kingdon, H. S.: Use of 3H-thymidine for measurement of DNA synthesis in rat liver—a warning. Analyt. Biochem. 45, 298–305 (1971)

    Google Scholar 

  • Ogur, M., Rosen, G.: The nucleic acids of plant tissue: I. The extraction and estimation of deoxypentose nucleic acid and pentose nucleic acid. Arch. Biochem. 25, 262 (1950)

    Google Scholar 

  • Rajewsky, M F., Fabricius, E., Hülser, D. F.: Synchronisation in vivo: Temporary inhibition of DNA synthesis in the rat embryo with hydroxyurea. Exp. Cell Res. 66, 489–492 (1971)

    Google Scholar 

  • Ritter, E. J., Scott, W. J., Wilson, J. G.: Teratogenesis and inhibition of DNA synthesis induced in rat embryos by cytosine arabinoside. Teratology 4, 7–14 (1970)

    Google Scholar 

  • Ritter, E. J., Scott, W. J., Wilson, J. G.: Relationship of temporal patterns of cell death and development of malformation in rat limb. Possible mechanism of teratogenesis with inhibition of DNA synthesis. Teratology 7, 219–226 (1973)

    Google Scholar 

  • Schmidt, G., Tannhauser, S. J.: A method for determination of deoxyribonucleic acid, ribonucleic acid and phosphorproteins in animal tissues. J. biol. Chem. 161, 83–89 (1945)

    Google Scholar 

  • Schneider, W. C., Greco, A. E.: Incorporation of pyrimidine deoxyribonucleosides into liver lipids and other components. Biochim. biophys. Acta (Amst.) 228, 610–626 (1970)

    Google Scholar 

  • Scott, W. J., Ritter, E. J., Wilson, J. G.: DNA synthesis inhibition and cell death associated with hydroxyurea teratogenesis in rat embryos. Develop. Biol. 26, 306–315 (1971)

    Google Scholar 

  • Skoog, L., Nordenskjöld, B.: Effects of hydroxyurea and 1-β-d-arabinofuranosylcytosine on deoxyribonucleotide pools in mouse embryo cells. Europ. J. Biochem. 19, 81–89 (1971)

    Google Scholar 

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This work was supported by grants from the Deutsche Forschungsgemeinschaft given to the Sonderforschungsbereich 29, “Embryonale Entwicklung und Differenzierung Embryonal-Pharmakologie”.

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Krowke, R., Bochert, G. Inhibition of RNA synthesis, a possible mode of the embryotoxic action of hydroxyurea. Naunyn-Schmiedeberg's Arch. Pharmacol. 288, 7–16 (1975). https://doi.org/10.1007/BF00501810

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  • DOI: https://doi.org/10.1007/BF00501810

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