Introduction: Genotoxicity of chemical compounds is primarily associated with the interaction with DNA, formation of mutations, damage to chromosomes and initiating carcinogenesis processes. Currently, many compounds found in the environment are considered to be genotoxic agents, among them...

Background. The interaction of environmental factors with genetic susceptibility and detoxification level seems to be an important causative factor in bladder cancer (BC). The aim of this study was to look for a BC marker panel which reflects the environmental risk. The nuclear matrix protein 22 (NMP22), bladder cancer-4 (BLCA-4), and total level proteins NMP22 and BLCA-4 (NMBL) in BC patients with genetic predisposition NAT2 (classified as slow acetylators, SA), DNA damage (8-OHdG), and detoxification by isoenzyme GSTπactivity were measured.Materials and Methods. The urine and blood from 91 BC patients and controls were examined, also according to tumor stage (T) and grade (G). The participants completed a questionnaire in order to evaluate environmental risk.Results.Most patients (75.3%) were previous or actual smokers. The levels of 8-OHdG, NMP22, BLCA-4, NMBL, and GSTπwere significantly higher in BC (p≤0.001). The majority of patients (59.3%) were slow acetylators (SA). The highest BLCA-4/8-OHdG correlation was observed in total BC and SA smokers.Conclusions.The total pool of nuclear matrix proteins in the urine (NMBL) has a higher diagnostic value in bladder cancer than single proteins. The particular value of BLCA-4 and GSTπin the aspect of environmental risk was noted.

Occupational and environmental exposure to xenoestrogens, a subgroup of endocrine disruptors (EDCs), can affect the endocrine system and increase the risk of cancer, primarily the hormone-dependent kind. This type of cancer includes ovarian cancer, which is the leading cause of death from gynecological tumors. The aim of this study was to assess the role of 17β-estradiol and its metabolites: 2-MeOE2, 16α-OHE1 in exposure to the metalloestrogen cadmium. The effect of interactions of cadmium with estrogens on the viability of cells in malignant ovarian cancer cells SKOV-3 was investigated, both in simultaneous action and in the pre-incubation model. There are no known interactions between estrogens and cadmium in ovarian cancer cells. Due to the frequent occurrence of multidrug resistance (MDR) in ovarian cancer, the effects of estrogens and cadmium on MDR in SKOV-3, measured as P-glycoprotein (P-gp), were assessed. An interaction study showed that E2 had an antagonistic effect on cadmium-induced cell damage, while 2-MeOE2 showed less of a protective effect in combination with CdCl₂ than E2. There were two types of interaction: toxic synergism and beneficial antagonism. E2 and cadmium increased P-gp expression in SKOV-3 cells, while 2-MeOE2 decreased P-gp expression to a potentially beneficial effect on MDR prevention. The obtained results constitute an interesting starting point for further research in the field of interactions between estrogens and xenoestrogens in ovarian cancer.

Breast cancer is the most common cancer occurring in women and causing the highest number of deaths among them. The role of xenoestrogens has been the subject of many studies in the pathogenesis of breast cancer. Less is known about the impact of xenoestrogens on the effectiveness of hormone therapy used to treat breast cancer, and thus possible drug-xenostrogen interactions. The aim of this review is to summarize the current state of knowledge and present perspectives for further research on the impact of xenoestrogens on the effectiveness of drugs used in the treatment of hormone-dependent breast cancer. Phytoestrogens, in particular flavonoid genistein, are the best studied group of xenoestrogens in terms of interaction with drugs used in the treatment of breast cancer, due to their frequent use, including their use in alleviating the adverse effects of hormone therapy. Analyzing the current state of knowledge, it seems that phytoestrogens intake should be avoided during conventional anti-cancer treatment. Of the other xenoestrogens, bisphenol A (BPA) is one of the best-tested compounds for interactions with drugs used to treat breast cancer. It has been shown that bisphenol A could reduced therapeutic effect of active tamoxifen metabolite and cytostatics used in breast cancer treatment. Confirmation in clinical trials of the results obtained in vitro and in vivo tests, would enable the creation of specific recommendations for patients undergoing breast cancer treatment, especially hormone therapy. An area requiring further research is the analysis of the effects of xenoestrogens other than phytoestrogens, e.g. metalloestrogens, on the effects of drugs used in the treatment of breast cancer.

Ovarian cancer is the leading cause of death from gynecologic malignancies. Some estrogens, as well as xenoestrogens, such as chromium (VI) (Cr(VI)), are indicated as important pathogenic agents. The objective of this study was to evaluate the role of estradiol and some its metabolites upon exposure to the metalloestrogen Cr(VI) in an in vitro model. The changes in cell viability of malignant ovarian cancer cells (SKOV-3 resistant to cisplatin) exposed to 17β-estradiol (E2) and its two metabolites, 2-methoxyestradiol (2-MeOE2) and 16α-hydroxyestrone (16α-OHE1), upon exposure to potassium chromate (VI) and its interactions were examined. The single and mixed models of action, during short and long times of incubation with estrogens, were applied. The different effects (synergism and antagonism) of estrogens on cell viability in the presence of Cr(VI) was observed. E2 and 16α-OHE1 caused a synergistic effect after exposure to Cr(VI). 2-MeOE2 showed an antagonistic effect on Cr(VI). The examined estrogens could be ranked according to the most protective effect or least toxicity in the order: 2-MeOE2 > E2 > 16α-OHE1. Early pre-incubation (24 h or 7 days) of cells with estrogens caused mostly an antagonistic effect—protective against the toxic action of Cr(VI). The beneficial action of estrogens on the toxic effect of Cr(VI), in the context of the risk of ovarian cancer, seems to be important and further studies are needed.