The influence of selected cytostatics on human trophoblast in vitro.
The effect of cytostatics (Methotrexate, Oncovin and Dactinomycin) on early human trophoblast in vitro was studied by the tissue (organ) culture technique according to Trowell and by brief incubation with thymidine 3H. The cytostatics were tested by the method of Tanneberger in clinical and tenfold higher doses. The criteria for cytostatic efficacy were based an activity of DNA, histologic and histochemical changes, and secretion of hormonal chorionic gonadotropin. In vitro cultures of trophoblast were found to be a good model for evaluation of cytostatics, and the tested chemotherapeutics were effective chemotherapeutically. Upon addition to in vitro cultures they changed the structure and function of trophoblastic cells, resulting in depression of DNA resynthesis, histologic changes, changes in enzyme activities assessed histochemically, and impaired HCG secretion. The most pronounced effects were obtained with Dactinomycin or with a combination of Dactinomycin and methotrexate. Methotrexate alone had the weakest effect on DNA resynthesis and structure of the trophoblastic cells. The effect achieved with methotrexate after 120 hours was equal to the effect of Dactinomycin after 48 hours. Comparison of the histologic and hormonal results with DNA activity showed concordance between the intensity of morphologic and hormonal changes and impairment of nucleic acid functions.
D000135:Acid Phosphatase / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology; D014750:Vincristine / Q000494:pharmacology*
D006063:Chorionic Gonadotropin; D003609:Dactinomycin; D014750:Vincristine; D006913:Hydroxysteroid Dehydrogenases; D005954:Glucosephosphate Dehydrogenase; D000135:Acid Phosphatase; D008727:Methotrexate