Some characteristics of the mechanism of action of copper (II) complexes with alpha-amino acids

On the basis of the supposed difference in the mechanisms of action of copper (II) complexes with alpha-amino acids and of alkylating agents, the antitumor activity of Cu-2 when given in conjunction with cis-diamminedichloroplatinum (DDP) is studied. The DNA precursor C 14-thymidine was injected into mice 30 min before sacrifice. Doses of the substances appropriate as regards toxicity were used: Cu-2 9 mg/kg, DPP 4 mg/kg. The antitumor effect was assessed as inhibition of tumor growth, calculated relative to the mean volumes of the tumor in the experimental animals, was compared with the controls over a period of time. Toxicity was recorded as the percentage of mice which died and changes in the mean weight of the spleen. The investigations show that Cu-1 does not induce direct inhibition of DNA synthesis in the tumor cell, unlike DDP and sarcolysin. Combined administration of Cu-2 and DDP leads to summation of their antitumor effect without any increase in toxicity