INVESTIGATION OF THE TRANSMEMBRANE POTENTIAL OF MITOCHONDRIA AND THE GENERATION OF FREE RADICAL COMPOUNDS IN LYMPHOCYTES OF CERVICAL CANCER PATIENTS

Abstract

Summary. Important indicators that reflect changes in the functional state of non-malignant cells from the tumor environment and can be used as predictors of the occurrence of complications as a result of radiation and chemo radiation therapy are the level of polarization of the mitochondrial membrane and the intensity of production of reactive forms of oxygen and nitrogen (free radical compounds, FR). Aim: To investigate changes in the mitochondrial transmembrane potential (MTP) and the intensity of FR formation in peripheral blood lymphocytes (PBL) of cervical cancer (CC) patients before the chemo radiation therapy. Object and methods: In the study used peripheral blood samples of 26 patients with СС before starting chemo radiation therapy and 29 apparently healthy individuals (AHI, control group). PBL isolation was performed on Histopaque®-1077. The level of TMP in lymphocytes was determined using the dye JC-1, the intensity of FR formation using the dye DCFH-DA. Results: It was shown that the tendency to lower TMP (by 1.46 times) and significantly lower FR formation (by 2.84 times) was observed in the PBL of patients with CC. In the examined patients with a greater degree of the size of the primary tumor and its’ invasion (T2 compared to T1) or a greater degree of tumor differentiation (G2 compared to G2/3-3), the TMP level was higher (by 1.35 and 1.47 times, respectively). In CC patients, in contrast to AHI, a significant correlation was found between the TMP level and the intensity of FR formation (r=0.473). It has been shown that in the PBL of CC patients with the stage of the tumor process T1N0M0 and the degree of the tumor differentiation G2, the level of TMP and the intensity of BP formation are significantly lower (by 1.91 times and 1.88 times, respectively) than in similar patients with uterine cancer, who has been examined before. Conclusions: The functioning of lymphocytes of patients with CC before chemo radiation therapy is already changed according to the indicators of TMP value and FR formation, which are significantly lower than in AHI lymphocytes. In contrast to the control group, a significant correlation was found between the TMP levels and BP formation in the PBL of the examined CC patients. It has been shown that in CC patients with a disease stage of T1N0M0 and a G2 tumor differentiation degree changes in the level of TMP and the FR formation are more pronounced than in a similar group of patients with uterine cancer. The obtained results are background for evaluating the changes occurring in the cells from the tumor environment after radiation therapy.