Comparative analysis of mitochondrial free radical markers in endometrioid adenocarcinoma and an experimental model.

e17627 Background: Endometrial cancer (EC) is the sixth most common cancer worldwide. In postmenopausal women, adipose tissue converts androgens to estrogens. Estrogen has antioxidant functions, protecting cancer cells from reactive oxygen species. Mitochondria can be exposed to free radicals, leading to increased DNA mutations. This paper presents clinical and experimental data from a comparative study, drawing parallels between alterations in free radical processes observed in the mitochondria of uterine and tumor cells from female patients and rats. The aim was to study parameters of free radical processes in the mitochondria of endometrioid adenocarcinoma (EA) cells from gynecologic oncology patients and in the mitochondria of intrauterine Guérin carcinoma cells in rats. Methods: The study included 42 patients who underwent surgery for EA and 14 patients with uterine fibroids (source of intact endometrium). Among the EA patients, 16 had well-differentiated (G1), 12 had moderately differentiated (G2), and 14 had poorly differentiated (G3) EA. The mean age of EA patients was 60.8±2.9 years; for those with fibroids, it was 49.4±2.5 years. Patients did not receive neoadjuvant therapy. The experimental part utilized biological material from 15 outbred laboratory female rats (250±25 g) with modeled intrauterine growth of Guérin carcinoma. In mitochondria isolated from tumor tissue and intact uterine tissue, concentrations of mitochondrial superoxide dismutase (SOD-2), malondialdehyde (MDA), diene conjugates (DC), and oxidative DNA/RNA modification products were determined using enzyme-linked immunosorbent assay (ELISA). Protein was measured via the Lowry method. Statistical analysis used parametric and nonparametric tests with adjustments for multiple comparisons. Results: In patients, mitochondria from G1 EA cells showed high levels of MDA and DC, which were 2.3-fold and 2.9-fold higher, respectively, compared with intact endometrium. In G2 tumors, MDA levels were 3.2 times higher, and DC levels were 2.7 times higher than in intact mitochondria. G3 tumors exhibited a 1.6-fold increase in DNA damage (p<0.05), along with 2.4-fold, 3.0-fold, and 3.4-fold increases in MDA, DC, and SOD-2 concentrations, respectively, versus intact tissue. In female rats, tumor mitochondria exhibited changes analogous to those in EA patients: MDA increased 1.6-fold (p<0.05), DC 1.5-fold (p<0.05), SOD-2 2.4-fold, and DNA damage 1.6-fold (p<0.05) compared with intact uterine tissue values. Conclusions: Oxidative stress and mitochondrial dysfunction in malignant cells from patients indicate a pathogenetic feature dependent on the degree of tumor differentiation. The experimental model confirms the association between free radical processes and mitochondrial alterations, likely contributing to the pathogenetic mechanism of uterine carcinoma.