FEATURES OF OXIDATIVE METABOLISM AND GENETIC DISORDERS IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH PRIMARY CERVICAL CANCER.

Abstract

Background: The combination of chemo- and radiotherapy used as main treatment of locally advanced cervical cancer (CC) may lead to side effects in healthy cells, which undermine the effectiveness of treatment and quality of life. The assessment of damage level in healthy radiosensitive cells from the tumor environment before the treatment is important in order to predict and prevent remote side effects of radiation.

Aim: To study the oxidative metabolism and genetic disorders in peripheral blood lymphocytes (PBL) of primary CC patients in order to evaluate the possibilities of predicting radiation complications based on the molecular and biological properties of PBL.

Materials and methods: Peripheral blood samples were collected from 13 primary CC patients T1-4N0-1M0-1, and PBL were routinely isolated. The oxidative metabolism (mitochondrial trans-membrane potential, superoxide anion radical (О2•) generation, reactive oxygen species (ROS) production in PBL as well as the level of SH-groups in plasma and pro/antioxidant ratio in hemolysates were examined. The development of genetic instability was determined by estimation of DNA double-strand breaks (DNA-DSB), frequency and spectrum of chromosome aberrations and apoptosis.

Results: The marked increase in the intensity of О2• generation in PBL (1.5-fold), depletion of SH-groups content (1.6-fold) and a shift in the pro-antioxidant balance (1.4-fold) towards its prooxidant component were observed in the blood of primary CC patients as compared to healthy individuals. These oxidative stress related events were accompanied by an increase in the level of DNA-DSB (2.1-fold), apoptosis (3.5-fold) and frequency of cells with chromosome aberrations (3.9-fold). On the contrary, significant decrease in mitochondrial trans-membrane potential (2.0-fold) and ROS generation in PBL (4.0-fold) were detected.

Conclusion: Preliminary data indicate a violation of redox processes regulation, a shift in the pro-antioxidant balance towards its pro-oxidant component, accompanied by an increase in the level of DNA damage, development of genetic instability and apoptotic death of blood lymphocytes in primary CC patients.