Embriyonik kök hücre modeli kullanılarak etefonun gelişimsel toksisitesinin değerlendirilmesi

Mohammadi Nejad S. Evaluation of Developmental Toxicity of Ethephon Using Embryonic Stem Cell Model. Hacettepe University, Graduate School of Health Sciences, Pharmaceutical Toxicology Program, Doctor of Philosophy Thesis, Ankara, 2018. Ethephon, a member of the organophosphorous compounds, is one of the most widely used plant growth regulators for artificial ripening. In recent years, the developmental toxicology studies have increased due to a broad interest in neurodevelopmental problems. Concerning this, new in vitro screening models such as embryonic stem cells have been established in predictive toxicology to decrease the expense and time of the experiments number of laboratory animals. The goal of this study was evaluation of the neuro-developmental toxicicity potential of "ethephon". For this purpose, the mES cells were exposed to ethephon and the cytotoxicity, cell cycle, total antioxidant capacity, reactive oxygen species (ROS) and, expression of specific pluripotential genes including Oct-4, SOX2, NANOG, Nrf2, Nestin and neural differentiation genes such as MAP2 and β-Tubulin III were examined. Additionally, effects of ethephon on expression of stemness genes were assessed before and during neural differentiation. Our results from MTT assay with mEs cells, after 24, 48 and 96 h exposure to ethephon demonstrated that at higher doses (1280, 2560 and 5120 µM) ethephon is cytotoxic for mES cells. According to results of oxidative stress assays, it is suggested that the cytotoxic effect of ethephon is not related to the oxidative stress mechanism. In order to genetic evaluation, ethephon treated mES cells were analyzed before and after neuronal-differentiation by Real-time PCR. The expressions of several genes were evaluated. Our observations showed that ethephon is potent to induce a significant difference in expression of these genes in neuronal differentiated cellsFuture studies are necessary to understand the exact mechanism of developmental toxicity of ethephon. Key Words: Ethephon, cytotoxicity, stemness genes, developmental toxicity, neural differentiation.