Effects of some polyamines, polyanions and antitumor drugs on replicative DNA synthesis and unscheduled DNA synthesis in vitro.

The effects of various compounds on replicative DNA synthesis in permeable mouse ascites sarcoma cells and on unscheduled DNA synthesis in permeable cells or in isolated rat liver nuclei were studied. Polyamines such as spermidine, putrescine and cadaverine inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by spermidine and cadaverine, but slightly stimulated by putrescine at low concentrations. Aurintricarboxylic acid, a low molecular weight polyanion, inhibited both replicative DNA synthesis and unscheduled DNA synthesis. Replicative DNA synthesis was inhibited by heparin, a high molecular weight polyanion, whereas unscheduled DNA synthesis was stimulated at low heparin concentrations. Antitumor drugs such as daunomycin, neocarzinostatin and bleomycin inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by daunomycin, slightly induced by neocarzinostatin and highly induced by bleomycin. The present system was thought to be useful for studying the separate effects of various drugs on either replicative DNA synthesis or unscheduled DNA synthesis in vitro.