Evaluation of cytotoxicity, mutagenicity and genotoxicity of the herbicides tebuthiuron and trifluralin and its effects on expression of cellular stress responses genes

• Grant number: 12/15220-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2012
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Daniel Junqueira Dorta
• Grantee: Mariana Furio Franco Bernardes
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 14/02170-3 - Investigation of the effects of herbicides Trifluralin and tebuthiuron in activation of the signaling pathway to oxidative stress defense Keap1/Nrf2- are, BE.EP.DR

Abstract

The emerging contaminants are a new category of xenobiotics widely distributed in the environment. These contaminants include pesticides, which include herbicides, a heterogeneous category of chemical products, designed to control weeds. They can be grouped according to their mechanism of action and chemical structure. Tebuthiuron belongs to substituted ureas chemical group and its mechanism of action is by inhibition of photosystem II of photosynthesis. It is widely used in sugar cane crops. Trifluralin belongs to dinitroanilines chemical group and its mechanism of action is by inhibition of cell division by inhibiting microtubule formation. It is used, among other crops, in soybean plantations. Although some herbicides are described as selective in their mechanism of action, their range selectivity is limited in some animals tested. Thus, the study of these compounds is extremely important. In order to assess the cytotoxic effects of the herbicides tebuthiuron and trifluralin, we will use HepG2 cell culture to analyse cell proliferation, cell viability, interference with mitochondrial membrane potential, induction of nuclear condensation and fragmentation, exposure of phosphatidyl serine on the outer cell membrane, measuring the activity of caspases 9 and 3 cell and determination of production and accumulation of hydrogen peroxide (H2O2). To assess the mutagenic effects, we will use HepG2 cell culture to perform the comet assay and micronucleus test, and we will use Salmonella thyphinurium strains TA 98 and TA 100 to perform the Ames test. We will also perform molecular assays in HepG2 cells by Western blotting of the release of pro-apoptotic proteins such as cytochrome c and by PCR Array for the evaluation of the expression of cellular stress responses genes.

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)

FRANCO-BERNARDES, MARIANA FURIO; ROCHA, OTAVIO PELEGRINO; PEREIRA, LILIAN CRISTINA; TASSO, MARIA JULIA; MEIRELES, GABRIELA; DE OLIVEIRA, DANIELLE PALMA; DORTA, DANIEL JUNQUEIRA. The herbicides trifluralin and tebuthiuron have no genotoxic or mutagenic potential as evidenced by genetic tests. Environmental Science and Pollution Research, v. 24, n. 30, p. 24029-24037, OCT 2017. (12/15220-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BERNARDES, Mariana Furio Franco. Evaluation of cytotoxicity, mutagenicity and genotoxicity of the herbicides tebuthiuron and trifluralin and its effects on expression of cellular stress responses genes. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.