[Effect of rubomycin and its paramagnetic analog on DNA synthesis].

Abstract

Ruboxyl, a paramagnetic analog of rubomycin, was synthesized and subjected to a preliminary investigation at the Institute of Chemical Physics of the Academy of Sciences of the USSR. The drug is characterized by a higher antitumor activity, broader spectrum and lower general and cardiac toxicity. This is the first attempt of comparative biochemical investigation of rubomycin, ruboxyl and the nitroxyl radical at the level of DNA replication. The effect of these drugs on the synthesis of DNA in the cells of leukemia P-388, the bone marrow and heart of mice was studied. It was shown that the degree and duration of the DNA synthesis inhibition in the tumor cells correlated well with the antitumor activity of the drugs. On the 3rd day after administration rubomycin and ruboxyl induced stimulation of the DNA synthesis in the cells of the bone marrow. This might be explained by transfer of a part of the population of the bone marrow cells from Go phase due to the cytotoxic damages of the proliferating cells. The DNA synthesis stimulation in the bone marrow was most likely associated with the toxic effect of the drugs. No correlation between the cardiotoxicity and inhibition of the DNA synthesis in the heart cells of the mice was observed. The nitroxyl radical showed no biological activity on this model. The average lifespan of the mice treated with the nitroxyl radical was the same as that of the control animals. A decrease in the incorporation of 2-14C-thymidine into DNA of the tumor, bone marrow and heart was observed in the tumor carriers with development of the tumor.