Formation of nitric oxide metabolites during growth of transplanted tumors with different metastatic potential

Abstract

The dynamics of the endogenous production of NO metabolites, nitrites, nitrates, and volatile nit rosamines, has been investigated in the body, a tumor tissue, and peritoneal macrophages of mice F1 (C57Bl × CBA), Balb/c and BDF with subcutaneously transplanted tumors: Ehrlich carcinoma (EC) and Lewis metastatic lung carcinoma (LC). It has been shown that during the first three weeks, growth of EC is accompanied by a statistically significant increase in the total concentration of NO metabolites (NOx; nitrites + nitrates) up to levels (7.3 ± 3.49) × 10 -6 -(7.8 ± 2.57) × 10 -5 mol/kg in the tumor tissue and a sharp increase in NOx excretion with urine. At the same time, in the LC tumor tissue the maximal level of NOx (3.6 ± 0.46) × 10 -5 mol/kg was registered on day 7, and later it decreased demonstrating negative correlation with the tumor mass. At the stage of intensive LC growth (14, 21 days) there was significant inhibition of nitrite secretion by peritoneal macrophages. In all the controlled time intervals the EC tumor tissue con tained carcinogenic N nitrosodimethylamine and N nitrosodiethylamine; however, their concentrations significantly varied. Thus, the ability of the tumor tissue to produce NO metabolites was more pronounced in EC than in LC and depended on the time parameters of tumor growth.

Modulation of the formation of active forms of nitrogen by ingredients of plant products in the inhibition of carcinogenesis

“…Концентрации NO, продуцируемые iNOS, могут в 1000 раз и более превышать уровни NO, продуцируемые конститутивной eNOS (10 -9 -10 -8 M) [29][30][31]. Транскрипционный фактор NF-κB играет ключевую роль в регуляции генов, участвующих в воспалительных и иммунных реакциях, включая iNOS.…”

“…NO может как индуцировать, так и тормозить рост опухолей, выступая в последнем случае как соединение, перспективное в терапии опухолей [44]. Исследователи уделяют особое внимание роли iNOS в опухолевом процессе вследствие высокой продуктивности фермента в течение продолжительного времени (часы, дни) [29,45,46]. Полагают, что направленность физиологического ответа клетки существенно зависит от концентрации NO, которая может изменяться тысячекратно от nM до μM уровней.…”