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USE OF 3D CELL CULTURES AS AN ALTERNATIVE TOOL IN THE ASSESSMENT OF AUTOPHAGY/MITOPHAGY INDUCED BY EMERGING CONTAMINANTS

Grant number: 15/15742-8
Support Opportunities:Regular Research Grants
Start date: April 01, 2016
End date: March 31, 2018
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal Investigator:Daniel Junqueira Dorta
Grantee:Daniel Junqueira Dorta
Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers:Danielle Palma de Oliveira

Abstract

Currently, the development and optimization of alternative methods follows a strong international trend as an alternative to the use of animals in research. Among the new technologies being developed, there are different types of three-dimensional culture (3D) of cells that reproduce more reliably the in vivo environment then monolayers culture. Within this context, our research group, which already has great experience on the cytotoxicity and genotoxicity evaluation of xenobiotics, recently started using 3D cultures of liver cells and equivalent skin model. So we propose the implementation of 3D hepatic model to evaluate autophagy/mitophagy induction in presence of brominated flame retardants, environmental contaminants class with little information about its toxic mechanisms. Our group already has great experience with polybrominated flame retardants, which our preliminary results indicate the importance of autophagy in cell death induction when these compounds are incubated with hepatic monolayer cells cultures, besides the already evidenced apoptosis process. Thus, this project proposes the implementation of cutting edge techniques in the Toxicology laboratory, as the 3D cell culture and the analysis of autophagy, which together will be able to provide important data for human risk assessment more reliably; besides to the contribution to the formation of specialized human resources. It is important to highlight that data about the toxic mechanism of action of these compounds in human are sparse and data about the autophagic process related to these compounds do not exist in the literature (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PEREIRA, LILIAN CRISTINA; DUARTE, FILIPE VALENTE; INACIO FERREIRA VARELA, ANA TERESA; ROLO, ANABELA PINTO; MARQUES PALMEIRA, CARLOS MANUEL; DORTA, DANIEL JUNQUEIRA. Exposure to BDE-153 induces autophagy in HepG2 cells. TOXICOLOGY IN VITRO, v. 42, p. 61-68, . (16/03950-8, 15/15742-8)