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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 277 (1973), S. 71-88 
    ISSN: 1432-1912
    Keywords: Cyclophosphamide ; Embryonic Development ; DNA-Dependent RNA Polymerases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On day 13+0 h of gestation rats received 10 mg/kg cyclophosphamide i.p. 3, 9, and 24 h after administration of the drug the activities of the DNA-dependent RNA polymerase reactions were measured in the whole embryo and in parts of it (head, upper and lower extremities and trunk). The activities of these enzymes were correlated with the increase in the RNA content of these tissues. A relationship was established light and electron microscopically between the biochemical results and the specific alterations which occur in different structures of the embryonic tissue. The results of these investigations show that: 1. cyclophosphamide leads-in dependency on the time-to a decrease or increase in the Mn++- and/or Mg++-stimulated RNA polymerase reactions in isolated cell nuclei of individual parts of the embryo 2. alterations in the enzyme activities of individual parts of the embryo are not detected when the enzyme activity of the whole embryo is measured at the early day 13 of gestation 3. towards the end of gestation malformations can be demonstrated only in those parts of the embryo, where 24 h after the administration of cyclophosphamide the enzyme pattern shows a highly significant deviation from that of the controls and where cell necroses can be demonstrated light and electron microscopically. Moreover, in the nucleolus of the neuroepithelium segregation of its components takes place which correlates well with the decreased r-RNA polymerase activity. In this paper a disturbance of the transcription mechanisms is discussed as being the primary mode of action of cyclophosphamide in cell metabolism.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 31-44 
    ISSN: 1432-1912
    Keywords: Embryonic Development ; Actinomycin D ; DNA-dependent RNA Polymerases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to elucidate the phase specificity of the embryo-lethal and teratogenic action of actinomycin D (day 5–10 of gestation) rats received 3H-actinomycin D at different times of gestation. The distribution of the radioactivity in the fetus and the placenta was measured. Moreover, the effects of actinomycin D on the RNA polymerase reactions in isolated nuclei of the decidual and fetal tissue were studied. The biochemical results were correlated electron microscopically with specific alterations occurring in different structures of the total implantation sites. These studies show that the time-dependent embryo-lethal and teratogenic effects of actinomycin D result from a lesion of the embryo and the decidua. The effects of the decidua occur at an earlier time and are more pronounced as compared to those of the embryo. Since the decidua is significant for the nutrition of the embryo till closure of the yolk-sac and beginning of the yolk-sac circulation (day 10 of gestation), the direct effects of actinomycin D on the embryo are intensified by the lesion of the decidua. After day 10 of gestation till the beginning of the placental function 3H-actinomycin D passes over to the embryo. But the concentration-even after a dose of 1 mg/kg-does not suffice to inhibit in vivo RNA polymerase reactions in isolated nuclei.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 271 (1971), S. 103-110 
    ISSN: 1432-1912
    Keywords: Embryonic Development ; DNA Polymerase ; Hypophysectomy ; Sex Hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of estrone plus progesterone on embryonic survival were studied in hypophysectomised pregnant rats. Replacement therapy commenced 24 h prior to the ablation of the pituitary which was performed on day 6 of pregnancy. The number of viable fetuses was correlated with increasing amounts of progesterone from 24 to 84 mg/kg given in concert with a constant dose of 4 μg/kg estrone. As judged by the DNA content of the 14-day-old embryos, growth retardation was linked to the reduction of the progesterone levels. No visible malformations were recorded although the experimental period covered the phase of organogenesis. On the other hand, when measuring in isolated nuclei of 14-day-old rat embryos the activity of DNA polymerase, an enzyme the activity of which can be correlated to a certain extent to embryonic growth, it becomes obvious that after treatment with estrone in combination with low (24 or 36 mg/kg) or too high doses (84 mg/kg) of progesterone the correlation between DNA content of the embryos and DNA polymerase activity per cell diverges. This result may point to a cellular malfunction not disclosed by the macroscopic appearance of the embryos at this stage. So it can be concluded that embryonic growth and differentiation processes might be directly dependent on maternal gonadal hormones, at least till day 12 of pregnancy.
    Type of Medium: Electronic Resource
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