Effect of Daunorubicin and Adriamycin on Nucleic ACID Synthesis of Serum Stimulated Mouse Embryo Fibroblasts

Abstract

This paper reports the effects of daunorubicin and adriamycin on DNA and RNA synthesis of in vitro cultured mouse embryo fibroblasts (MEF) stimulated by fetal calf serum (FCS). The addition of FCS to quiescent MEF cultures brings about a wave of RNA synthesis, followed by DNA synthesis which starts between 8 and 12 h after change of medium and proceed for up to 24 h. These cells are therefore partially synchronized. The level of DNA synthesis depends on the amount of FCS added. Daunorubicin and adriamycin are almost equally effective in inhibiting DNA synthesis, as well as cell proliferation, which takes place later. Adriamycin is more active than daunorubicin on RNA synthesis. In cultures treated for an 8 h period starting at different times after FCS addition, the highest DNA synthesis inhibition is achieved by treatment during the first 8 h, when DNA synthesis has not yet started. The cellular uptake of daunorubicin is constantly higher than that of adriamycin, in any experimental condition tested. The results show that FCS-stimulated MEF can provide a simple method for studying the effects of anthracycline antibiotics on partially synchronized cells.