MOLECULAR-BIOLOGICAL QUESTIONS IN THE CREATION OF THERAPEUTIC AGENTS AND STUDIES OF THEIR MECHANISMS OF ACTION THE NEW ANTITUMOR AGENT MORFOZOL: INTRACELLULAR DISTRIBUTION AND EFFECTS ON DNA SYNTHESIS

摘要

In vitro studies of the interaction of DNA with morfozol (a palladium (II) acid complex) demonstrated active binding with DNA, detected in terms of reductions in accessibility to actinomycin D. Extensive and stable inhibition of DNA synthesis was seen in LI210 and P388 leukemia cells; this was less marked in Akatol and B16 melanoma cells. Studies of the intracellular distribution of palladium in Akatol and P388 tumors after administration of Morfozol to tumor-bearing mice showed predominant accumulation in the cytosol fraction, which is evidence of an active interaction of the agent with cell proteins. I.p. administration of morfozol led to quite high palladium concentrations in the nuclear fraction. As morfozol is characterized by high reactivity, there are probably other targets, such as DNA polymerase and regulatory protein factors.