The features of enzymes activity to nucleoside and antioxidant systems in solid tumors

Abstract

Background. Solid tumors can create their aggressive properties. There are characterized by the invasion and metastatic activity, the resistance of the tumor clone to apoptosis. These pathways triggering may be realized both by 2-deoxy-D-ribose and its phosphorylated form (2-d-D-Rib-1-P), and by hydrogen peroxide.Aim. To investigate the peculiarities of enzymes activity to nucleoside metabolism and antioxidant system in epithelial tumors of different localization.Materials and methods. The features of the thymidine phosphorylase, adenosine deaminase, superoxide dismutase (SOD) and glutathione peroxidase (GPO) activity were studied in tumor homogenates. The visually no transformed tissues of the surgical resection edges were used as a control. Enzymes activity was determined by spectrophotometrical and morphological features were examined by the immunohistochemical methods in tissues of non-small cell lung cancer (NSCLC), samples of gastric and colon carcinomas (GCC).Results. Thymidine phosphorylase activity and adenosine deaminase activity in various malignant tumors were increased in comparison to the control. Respectively, thymidine phosphorylase activity was higher than by 1.8 times (p= 0.002 for NSCLC,p= 0.001 for GCC). An increase of adenosine deaminase activity was revealed both in tissues of NSCLC (more than 1.7 times) and in GCC (by 1.9 times,p= 0.001). No significant changes in SOD activity were detected in the tumors. GPO activity tended to decrease by an average of 1.3 times (p= 0.01 for NSCLC,p= 0.02 for GCC). A cluster analysis of the enzymatic activity features of the studied NSCLC tumors, as well as GCC, revealed their metabolic heterogeneity. According to its results, tumors of different localization were distinguished into 2 clusters. Common feature to their second clusters was an increase the SOD activity. It was accompanied by increase of thymidine phosphorylase activity (p= 0.045 for NSCLC,p= 0.049 for GCC). Therefore, both hydrogen peroxide and 2-d-D-Rib-1-P could be formed in them more intensively. It is important to note that morphological indicators of tumor aggression (decreased or lost expression of cell-cell adhesion marker, expression of mesenchymal markers, active angiogenesis) were detected more frequently in these subgroups.Conclusion. The obtained results reveal that individual features of the enzymes activity in epithelial tumors may be available source of 2-d-D-Rib-1-P and hydrogen peroxide generation in human cancer cells. In the case of individual higher tumor activity of thymidine phosphorylase and SOD and low GPO activity the metabolic stimulation of tumor progression may be occur.