INOS expression and biosynthesis of nitric oxide metabolites in the course of tumor growth of different histogenesis

Abstract

The dynamics of the production of nitric oxide (NO) metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs.