BIOMARKERS OF OXIDE-CARBONYL STRESS IN RATS WITH GUERIN’S CARCINOMA DURING THE TUMORS PROGRESSION DEPENDING ON SENSITIVITY TO CISPLATIN

Makovetska L.I., Sarnatska V.V.

• RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine

Aim: to investigate changes in markers of oxidative-carbonyl stress during the progression of Guerin’s carcinoma with different sensitivity to cisplatin and to establish their relation with molecular-structural changes of blood plasma albumin. Object and methods: the work was performed on Wistar rats (females aged 2.5 months and weighing 180–200 g) with transplanted cisplatin-sensitive or -resistant strains of Guerin’s carcinoma. The biological material for the analysis was taken on days 3, 5, 7, 9, 14, 18 and 21 after the implantation. In the research, there were determined prooxidant-antioxidant ratio and catalase activity in the hemolysate, the content of malonic dialdehyde (MDA) in the blood plasma, the content of free SH groups and fructosamine in the albumin molecule and the concentration of aldehyde dinitrophenylhydrazones in the blood plasma albumin fractions. Conformational changes occurring in the plasma albumin molecule were evaluated by absorption and fluorescence spectroscopy. Results: in the dynamics of carcinoma growth, there was detected an increase (compared with the intact control) in the pro-antioxidant ratio which had two peaks that were associated with the onset of active tumor growth on days 5, 18 (sensitive strain) and 9, 21 (cisplatin-resistant strain) after the transplantation. Throughout the experiment, an intensification of lipid peroxidation in the blood plasma of the tumor-bearing rats against gradual decrease in the catalase activity of the hemolysates was observed. The highest values of MDA were registered since day 9 until 21 after the tumor transplantation in the group of rats bearing cisplatin-resistant strain. There was shown a decrease in free sulfhydryl groups alongside with an increase in oxidative modification, glyoxidation end products and polymer cross-linked amyloid-type β-structures in the albumin pool of the rat blood plasma depending on the stage of development and the type of Guerin’s carcinoma strain. Significant changes in the molecular conformation of the albumin of the rat’s blood plasma in accordance with the external microenvironment formed in the blood plasma were observed. Conclusions: the obtained data suggest the presence of progressive oxidative carbonyl stress in rats with Guerin’s carcinoma which can be considered both as a trigger of tumor development and as an acquisition of high malignancy by neoplastic cells. The relation between oxidative carbonyl stress and molecular and structural changes of blood plasma albumin was demonstrated. The results can be used to improve the differential diagnosis of tumors, and the studied indicators can enrich the panel of non-tumor markers of the tumor development and the disease course.