THE REDOX-STATE INDICES OF BREAST ADIPOSE TISSUE IS IMPORTANT FACTOR OF TUMOR MICROENVIRONMENT IN PATIENTS WITH BREAST CANCER

Vovk A.V., Lukin S.M., Sydorchuk O.I., Virko S.V.

Breast adipose tissue (BAT) is a heterogeneous population of cells, which is represented by adi­pocytes and their precursors, endothelial cells, macrophages, pericytes. Due to the diversity of functions of superoxide radicals (SR), nitric oxide (NO), steroid hormones produced by its cells, BAT can affect the development and progression of breast cancer (BC). Objectives: the study of the levels of redox state indices of BAT in patients with triple negative (TN) BC with type II diabetes mellitus. Materials and me­thods: the samples of adjacent to the BAT (1 cm) were stu­died in 39 patients with TN BC II–III stage with normoglycaemia (n = 23) and type 2 diabetes mellitus (n = 16). According to the indicator of the ratio of the BAT volume to the total breast (7 ÷ 56%, median 21%) the patients were divided into 2 groups: the BAT volume < 21% and > 21%. Determination of the activity of cytochrome P450, the content of NO and the rate of generation of SR in BAT was carried out by the method of electron paramagnetic resonance. The level of oxidative damages of DNA (8-охоdGu) in BAT was determined spectrophotometrically. The le­vel of adi­ponectin expression was detected by immunohistochemistry. Results: in patients with TN BC (normoglycaemia) with BAT volume > 21%, the increase in the rate of SR generation, the level of oxi­dative DNA da­mage and the total activity of cytochrome P450 were determined, with a decrease in the level of expression of adiponectin (1.7 times) and NO compared to patients with BAT < 21%. In patients with BC with a violation of carbohydrate metabolism (type 2 diabetes mellitus) with BAT > 21%, an increase in the rate of SR gene­ration, level of oxidative DNA damage, activation of the detoxification system (cytochrome P450), reduction of adiponectin and NO levels, compared to patients with BAT < 21% were observed. Conclusions: violations of the ratio of hormonal and genotoxic parameters in the BAT, which are defined as local (placement of adipocyte tissue in relation to the tumor) and systemic factors (carbohydrate metabolism disturbance), were revealed.