OXIDATIVE TRANSFORMATION OF MACROMOLECULAR STRUCTURES UNDER THE INFLUENCE OF NEOADJUVANT RADIOTHERAPY FOR RECTAL CACER

The aim of the study was to examine the system of parameters of proteins and lipids oxidative modifications in patients with rectal cancer during the course of neoadjuvant radiotherapy. Blood serum samples for biochemical parameters analysis were obtained from 43 patients (20 men and 23 women, the average age 57±8,5 years) with histologically verified diagnosis of rectum adenocarcinoma II-III stage (T2-4N0-2M0). All patients were treated at the department of the gastrointestinal tract tumors in Ivano-Frankivsk Regional Clinical Oncology Center. During the first phase of treatment, patients underwent preoperative course of distant gamma-therapy for the tumor to a total focal dose of 36-40 Gy (single focal dose – 2 Gy, 18-20 sessions, 5 sessions per week) without the using of radiomodification. According to our data, the activity of lipid peroxidation processes in the serum of patients with rectal cancer before the beginning of radiotherapy was increased compared with the control group of healthy people, including patients with small size tumors (length of less than 5 centimeters) and without the presence of metastasis (T2N0M0). At the time of hospitalization malondialdehyde and diene conjugates levels exceeded normal levels at 34-39 %. Content of primary and secondary products of lipid peroxidation in blood positively correlated with the duration of disease history, disease stage and tumor size, regardless of age and sex of patients. After the first session of gamma-therapy malondialdehyde and diene conjugates levels increased significantly in all patients, with an average under 5.36±0.35 mmol/l and 0.67±0.05 с.u., with no significant difference between the subgroups of patients with 0, I-st and the II-nd degree of radiotherapy toxicity according to WHO scale. Analysis of free radical stress markers in the serum showed a significant increase of their concentration during the neoadjuvant radiotherapy course. The levels of malondialdehyde and diene conjugates were highest in the subgroup of patients with II degree of radiotherapy toxicity, exceeding benchmarks respectively 1.8 and 2.5 times. The concentration of aldehyde-dynitrofenilhydrazones, which are the markers of the proteins fragmentation prevailed during the first radiotherapy sessions and relative predominance of ketone forms – markers of protein aggregation was observed later. The level of macromolecules oxidative damage indicators in general correlated with the severity of disease manifestations and radiotherapy complications, indicating their diagnostic value and direct contribution to the formation of rectal cancer clinical symptoms. Our data suggest that besides direct effects on tumor site radiotherapy causes the development of systemic oxidative stress with secondary lesions of macromolecular structures that form the basis of biological membranes, genetic apparatus and enzyme systems. The nature and extent of biochemical violations, which we have identified correspond to radiotherapy toxicity level, indicating their direct contribution to the formation of clinical symptoms and the necessity of their correction with the usage of pathogenesis-based drugs in some cases.