Effect of environmental nitric oxides on the antitumor resistance of rats

To evaluate the influence of exogenous nitric oxides (NOx) on the antitumor resistance of rats, and to compare the activity of enzymes influencing the level of free radicals upon normal conditions and tumor growth.

The growth kinetics of Guerin carcinoma (GC) was studied. NO inhalation was performed in special chamber for 16 h per day during 1 month before GC transplantation. Proliferative activity of nonstimulated lymphocytes (PANSL), functional activity of peritoneal macrophages (PM) and cytotoxic activity of natural killer cells (NK) were studied in vitro. Proliferative activity of lymphocytes from lymph nodes (BTLR) was studied upon administration of Concanavalin A in vivo. The activity of xanthine oxidoreductase (XOR) and the level of lipid peroxidation (LPO) in tumor tissues were also evaluated.

The inhalation of exogenous NOx results in toxic effect on the T-cells of immune system in vivo. Tumor growth was accompanied by activation of NK cells, PM and by decrease of proliferative activity of T-lymphocytes. The influence of NO accelerated the growth of tumor and was accompanied by the decrease of relative weight of thymus, peripheral lymph nodes and spleen 2.9, 2 and 1.5 fold, respectively; 4.9 fold increase of functional activity of PM; 2 and 2.3 fold decrease of PANSL and BTLR, respectively. In tumor tissue was observed 3.5 fold decrease of LPO level but the ratio of XOR isoforms increased by 18 fold mainly due to inactivation of xanthine dehydrogenase (XDH).

The relation between the NO inhalation, immune status and antitumor resistance has been evaluated. The prolonged action of exogenous NOx negatively influence T-cells of immune system and caused hyperactivation of PM, sharp decrease of XDH activity and LPO level, and accompanied by accelerated tumor growth in vivo.