[Anti-nitrosative system as a factor of malignant tumor resistance to cytotoxic effect of nitrogen monooxide].

Abstract

The inhibitory action of binuclear dinitrosyl iron complexes with glutathione on the growth of implanted solid tumor in BDF1 mice bearing Lewis lung carcinoma cells was found. The effect was induced by intraperitoneal injection of the binuclear dinitrosyl iron complexes to mice at a dose of 200 μM/kg daily on days 1-5 and 7-11. At the binuclear dinitrosyl iron complexes: free glutathione ratios of 1:1; and 1:10 in solutions, the inhibitory effect of the DNICs reached the level of 70% and 85%, respectively. When B-DNICs were not further infused, intensive tumor growth, a more rapid rate of tumor growth than control, was observed. The selective accumulation of DNICs as well as iron nitrosyl complexes of heme-containing proteins in tumors were detected by EPR method. The latter were found also in the tumors in control animals. Tumor growth delay in course of B-DNIC administration to the mice is supposed to be due to the elaboration of anti-nitrosative defense in tumor tissue in response to the action of NO released from B-DNIC.