During the life cycle aerobic organisms are exposed to a number of endogenous and exogenous sources of ROS. Present in low to moderate concentrations these reactive molecules play an important role in many physiological processes such as regulation of signaling cascades and gene expression. In high concentrations, ROS can oxidize cellular proteins, lipids and DNA, causing changes in structure and function, damage and even cell death. When the concentration of free radicals exceeds the physiological level, a cell is said to be in a state of oxidative stress. To prevent the onset and reduce the consequences of oxidative stress, living organisms have developed powerful antioxidant system (AOS). This system includes a set of mechanisms to maintain the level of free radicals in the narrow range between physiological and toxic concentrations. The most important enzyme components in AOS are: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). These enzymes are involved in the removal of ROS and participate in maintaining level of reduced glutathione, thus ensuring the preservation of physiological functions and inhibit the development of cell damage and disease. Because of such an important role of AOS, the regulation of the functional expression of its components is of particular importance for physiological and pathological processes in aerobic organisms. One of the most important regulatory molecules in this system is Nrf2 (NF-E2 related factor 2). Nrf2 is a transcription factor that induces expression of many cytoprotective proteins including antioxidant enzymes, and therefore play an important role in the regulation of oxidative stress. Previous studies have clearly demonstrated a link between oxidative stress and carcinogenesis. Cancer is a multistage process that develops over three stages: initiation, promotion and progression and oxidative stress is associated with each of them. Moreover, antioxidant profile is altered in cancer cells compared with healthy, normal tissue, so these molecules may be important biomarkers in the assessment of risk and the degree of carcinogenesis. Endometrial cancer is one of the three most common diseases of female reproductive organs. It has been shown that benign and premalignant changes precede the malignant transformation of the uterus, which is why these conditions may be considered as stages of carcinogenesis. Despite numerous studies, the molecular processes involved in multi-stage development of endometrial cancer are not yet fully known. Therefore, the aim of this dissertation was to examine the changes in expression of the four most important antioxidant enzymes in the blood and tissues of patients with benign, premalignant and malignant endometrial transformations, as well as the mechanism of their regulation by transcription factor Nrf2. In this research we used endometrial tissue and venous blood of patients diagnosed with: polypus endometrii, uterus myomatosus, hyperplasia simplex endometrii, hyperplasia complex endometrii and adenocarcinoma endometrii. Polypus endometrii and uterus myomatosus were considered as benign, while hyperplasia simplex and hyperplasia complex endometrii were considered as premalignant transformation of the uterus. After adequate sample preparation, we initially determined the total protein concentration in blood and endometrial tissue of all five groups of patients. Then we performed SDS PAGE electrophoresis, transfer to nitrocellulose membrane and chemiluminescent detection of CuZnSOD, CAT, GPx, GR and Nfr2 protein molecules. The protein levels were normalized with respect to β-actin. Furthermore, in endometrial samples of all five groups of patients, RNA was extracted and underwent reverse transcription into cDNA, followed by the TaqMan Real-Time PCR method by which the amounts of CuZnSOD, CAT, GPx, GR and Nfr2 mRNA were determined in respect to POLR2 as endogenous control. The results of these experiments showed the following: 1. In comparison to patients with polyps and myomas, in endometrium of women with hyperplasia simplex and hyperplasia complex decreased levels of Nrf2 were recorded, while in adenocarcinoma tissue Nrf2 protein level was increased. The observed changes were regulated at the transcriptional level, except in adenocarcinoma tissue in which increase in Nrf2 level was regulated by some post-transcriptional mechanism. 2. CuZnSOD mRNA level and the amount of CuZnSOD protein in the endometrium of patients with hyperplasia simplex and hyperplasia complex were decreased compared to patients with polyps and myomas. In adenocarcinoma tissue, however, the values of these parameters were significantly increased compared to both benign and both premalignant transformations. Observed transcriptional and translational CuZnSOD variability in different stages of endometrial transformation were the consequences of changes in the level of transcription factor Nrf2. 3. Compared to the control groups with polyps and myomas, levels of CAT mRNA and CAT protein were significantly decreased in the tissues of patients with premalignant and malignant lesions of the uterus. It is also shown that Nrf2 had no direct effect on the CAT gene transcription, but acting on other translational and posttranslational processes can probably influence the level of this enzyme in the endometrium. 4. During carcinogenesis, increase of GPx protein level was detected in premalignant endometrium, while decline in the the amount of this enzyme was measured in adenocarcinoma tissue. GPx level was positively correlated with the amount of transcription factor Nrf2, but mechanism that regulates the expression of this enzyme varied with the degree of tissue transformation. 5. In the course of malignant endometrial transformation, increased expression of glutathione reductase was observed. Consequent increased level of GR protein was the result not only of the intensified transcription under the influence of Nrf2, but also of an additional, posttranscriptional mechanism activated in transformed cells of the uterus. 6. As regards AOE expression in the blood of examined patients, it was observed that in comparison to the control group, in groups of women with benign endometrial changes a decline in Nrf2 and GR levels were measured, GPx level was increased, while the relative amounts of CuZnSOD and CAT protein did not change significantly. Somewhat more pronounced changes were observed in the blood of patients diagnosed with hyperplasia simplex, hyperplasia complex and adenocarcinoma, characterized by declined protein levels of Nrf2, CuZnSOD and GR, increased level of GPx and unaltered expression of CAT. It was also shown that the blood expression levels of all investigated AOE correlated positively with the amount of Nrf2. The results of this dissertation indicate the existence and importance of the specific expression pattern of antioxidant enzymes and transcription factor Nrf2 in gynecological patients diagnosed with: polypus endometrii, uterus myomatosus, hyperplasia simplex endometrii, hyperplasia complex endometrii and adenocarcinoma endometrii. The observed changes confirm the important role of the examined enzymes in complex molecular interactions that underlie the transformation of endometrial cells. It is obvious that these AO molecules not only influence the development of lesions in the uterine tissue, but they are also an important factor for the progression of benign changes in premalignant and malignant phenotype. It can be concluded that the results of this dissertation contribute significantly to a better understanding of the molecular processes involved in carcinogenesis. Implementation of this knowledge in clinical practice could contribute to the quality of prevention, diagnosis and treatment of gynecological patients, may lead to to improvement in the disease course and prognosis and, consequently, may result in increased survival rate of cancer patients. Tokom čitavog životnog ciklusa aerobni organizmi su izloženi brojnim endogenim i egzogenim faktorima koji indukuju povećanje produkcije ROS-a. Prisutni u fiziološkim koncentracijama, reaktivni molekuli ROS-a imaju značajnu ulogu u važnim ćelijskim procesima kao što su regulacija signalnih kaskada i genske ekspresije. U visokim koncentracijama ROS mogu oksidovati ćelijske proteine, lipide i DNK i time dovesti do promena strukture i funkcije, oštećenja, pa i smrti ćelije. Kada koncentracija slobodnih radikala premaši fiziološki nivo, smatra se da se ćelija nalazi u stanju oksidativnog stresa. Kako bi sprečili nastanak i umanjili posledice ove vrste stresa, živi organizmi su razvili moćan antioksidativni sistem zaštite (AOS). Ovaj sistem uključuje seriju mehanizama kojima se nivo slobodnih radikala održava u uskom opsegu između fiziološke i toksične koncentracije. Najvažnije enzimske komponente AOS su: superoksid dismutaze (SOD), katalaza (CAT), glutation peroksidaza (GPx) i glutation reduktaza (GR). Ovi enzimi uklanjaju višak ROS-a i učestvuju u održavanju nivoa redukovanog glutationa, čime obezbeđuju očuvanje osnovnih životnih funkcija i sprečavaju nastanak oštećenja i bolesti ćelije. Zbog tako važne uloge AOS, regulacija funkcionalne ekspresije njegovih komponenti je naročito značajna za fiziološke i patološke procese u aerobnim organizmima. Jedan od najvažnijih regulatornih molekula u tom sistemu je Nrf2 (NF-E2 related factor 2). Nrf2 je transkripcioni faktor koji indukuje ekspresiju mnogih citoprotektivnih proteina uključujući i antioksidativne enzime, zbog čega ima značajnu ulogu u regulaciji oksidativnog stresa. Savremena istraživanja na različitim model-sistemima ukazuju na povezanost oksidativnog stresa i kancerogeneze. Razvoj kancera je višestepeni proces koji se razvija kroz tri faze: inicijaciju, promociju i progresiju, a oksidativni stres je povezan sa svakim od ova tri stadijuma transformacije ćelije. Osim toga i sam antioksidativni p