[Mechanisms of the antitumor action of spirobromine in mice with leukemia P-388]. / Izuchgenie mekhanizma protivoopukholevogo deistviia spirobromina u myshei s leikozom P-388.

The influence of new antitumor drug, spirobromine, a derivative of dispirotripiperazine, on DNA synthesis in tumor cells and organs at different times after its injection into mice with P388 leukemia has been studied. The duration of DNA synthesis inhibition in tumor cells was found to correlate with spirobromine antitumor activity. A certain selectivity of action of the studied compound on DNA synthesis in P 388 leukemia cells as compared to the action on DNA synthesis in bone marrow, small intestine, spleen and liver of tumor animals was observed.

[Effect of rubomycin and its paramagnetic analog on DNA synthesis]. / Vliianie rubomitsina i ego paramegnitnogo analoga na sintez DNK.

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.

[Kinetics of macromolecular carbamoylation in normal and tumor cells after the administration of N-methyl-N-nitrosourea-14CO]. / Kinetika karbamoilirovaniia makrokolekul normal'nykh i opukholevykh kletok posle vvedeniia N-metil-N-nitrozomocheviny-14CO.

The pharmacokinetics of N-methyl-N-nitrosourea-14CO (14CO-MNU) was investigated in hepatoma 22a tumor-bearing and normal mice at various time after a single intravenous injection (80 mg/kg). The rapid clearance of 14CO-MNU from plasma of the mice was observed 5 hours following the administration of the drug. Peak levels of radioactivity in the hepatoma were noted 48 hours after the administration of 14CO-MNU, while the liver, kidney, spleen and intestinal epithelium showed an insignificant radioactivity at this time both in normal and tumor-bearing mice. The analysis of the radioactivity distribution among macromolecules (DNA, RNA, protein) and lipids indicated the highest label in lipids of all organs.