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Comparison of the toxicity of bisphenol A and bisphenol S individually and in association in HepG2 cells

Grant number: 16/07661-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2018
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal researcher:Fernando Barbosa Júnior
Grantee:Maria Fernanda Hornos Carneiro
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):16/23481-2 - Evaluation of the ability of coenzyme Q10 to counteract the effects upon meiosis and/or early embryogenesis of bisphenol A, dibutyl phthalate, 2-(thiocyanomethylthio)benzothiazole, permethrin, and N,N-diethyl-meta-toluamide in Caenorhabditis elegans, BE.EP.PD


Bisphenol A (BPA) is a chemical compound produced in large quantities widely used in the production of plastic, polycarbonates and epoxy resins, in order to make a variety of consumer products. The oral route is the most frequent way of exposure. In addition, BPA is metabolized primarily by the liver being excreted in urine. Studies have shown that human exposure to BPA can lead to obesity and diseases including diabetes, arteriosclerosis, genital malformations, liver disorders and cancers. BPA is known to be an endocrine disruptor with estrogenic activity that may affect the endocrine system and cause hormone-sensitive tumorigenesis. However, the mechanisms by which BPA exerts genotoxicity are still little known. Restrictions and regulations were created to impose limits on the use of this substance, but alternative bisphenol compounds with chemical structure similar and more stable to heat, such as bisphenol S (BPS), have been developed and are being used. Despite a reasonable knowledge of the toxic effects of bisphenol A, little is known about the toxicity of bisphenol S. In addition, there are no restrictions on the use of this compound. It should be noted that although are exposed to a mixture of toxicants, most studies have focused on the toxicological effects of an unique agent excluding possible effect of others in association. Thus, the identification of the potential toxic effect of such mixtures is a relevant topic. Considering BPA and BPS which have been suggested to have a carcinogenic potential, toxicity evaluation per se and in co-exposure is a topic still containing many gaps. The study aims to assess the effect of exposure to the BPA and BPS, individually or in association, upon cytotoxicity, genotoxicity, mutagenicity, apoptosis and DNA oxidative damage in HepG2 cells. For this, HepG2 cells will be exposed to BPA, BPS and BPA + BPS at different concentrations and evaluated for cytotoxicity (MTT assay), genotoxicity (comet assay), mutagenicity (citoma test), apoptosis (flow citometry) and formation of 8-hydroxydeoxyguanosine (ELISA). The results of the study will contribute to the establishment of the toxicological profile of BPA and BPS individually and as a mixture, especially regarding the potential genotoxicity of them and the possible mechanism of oxidative DNA damage.

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