Danila Cuomo
University of Sannio, Italy
Title: Toxicogenomics in dissecting the BPA activity in endoderm derived organs
Biography
Biography: Danila Cuomo
Abstract
Toxicogenomics accomplished to standard toxicology are considered a powerful method for low-dose endocrine disruptor compounds (EDCs) testing. In recent years, it has been developed a strong demand for reducing the use of small mammals in chemical testing. To meet this need, it is necessary to estimate the possibility of validly replacing them with cellular and no-mammal models. We explored this aspect investigating the activity of BPA as EDC in immortalized rat follicular cell line (FRTL-5), in primary pancreatic islets and hepatocytes, models for endodermal cells. In FRTL-5 environmental doses of BPA induce the transcription of thyroid specific genes and their transcriptional regulators. Furthermore, we highlighted the activation of NF-kB pathway in thyrocytes after BPA exposure. Basic on our data, we developed a reporter cell line able to sense BPA at very low concentrations. By gene expression analysis, we revealed that thyrocyte transcriptome reacts dynamically to low-dose BPA exposure. Particularly, we uncovered its capability to weaken cellular response to a further stress factor. Environmental exposure to BPA does not impact hepatocyte transcriptome. On the other side, the expression of few genes is altered in ex-vivo cultured pancreatic islets, leading to impairment of mitochondrial activity and apoptosis. Also in this case, the experimental activity highlighted that BPA exposure can alter cells ability to respond to damages. Overall, we propose new mechanisms for BPA toxicity that are exerted, exclusively, in presence of further stressors. This observation suggests revisions in the development of experimental plans including multiple exposure conditions.