Bisphenols (BPs) are a group of synthetic compounds used in the industrial production of polymers, particularly epoxy resins and polycarbonate plastics. They have versatile industrial applications and are present in numerous everyday products. Concerns about their impact on health have arisen with the widespread use of BPs. Numerous studies highlighting the adverse effects of Bisphenol A (BPA) have led to legislative regulations on its use, and increasing regulatory restrictions have resulted in the rapid development of BPA analogues. The toxicological profile of BPA analogues is not fully understood, and even less is known about the effects of complex mixtures of analogues. In toxicology, combined effects can have unwanted consequences for human health, making the study of chemical mixtures important for health protection. Due to the increasing use of BPA analogues and their growing presence in products and the environment, our master's thesis examined the influence of BPA, its analogues BPAP and BPC, and binary mixtures of BPA with BPAP and BPA with BPC on the growth, shape, and surface area of 3D cell models, developed from human hepatocellular carcinoma (HepG2) cells. We investigated their cytotoxic and genotoxic activities, as well as their impact on oxidative stress induction. The tests were conducted after short-term (24 hours) and long-term (96 hours) exposure. We found that the selected BPs and their mixtures did not cause any changes in the growth, shape, and surface area of the spheroids. Using the MTS and ATP tests, we determined that none of the tested BPs and their mixtures affected cell viability in the spheroids after 24 and 96 hours of exposure, except for BPAP at a concentration of 20 μM after 24 hours, where we observed reduced cell viability. By measuring the formation of malondialdehyde (MDA) and reactive oxygen species (ROS), we evaluated the impact of BPs and their mixtures on oxidative stress. We found that all tested BPs and mixtures induced the formation of ROS, with BPAP having the greatest impact on long-therm oxidative stress. Using the comet assay, we discovered that all BPs and their mixtures caused DNA single-strand breaks after short-term exposure, which was confirmed even after long-term exposure, except for the BPA + BPC mixture, which did not exhibit genotoxic effects. BPC showed the highest genotoxic potential, causing DNA breaks at concentrations of ⡥ 10 μM (24 hours) and 1 μM (96 hours). Based on the obtained results, we concluded that the BPA + BPAP mixture exhibited a synergistic genotoxic effect after 96 hours. Our findings contribute new knowledge to the missing data on the toxicity of BPA analogues and their complex mixtures, but further research is necessary due to the increasing production and presence of BPs.
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