Xenobiotic effects in cultured human cells and study of mechanisms of cytotoxic and genotoxic damage

• Grant number: 09/54816-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2010
• End date: February 29, 2012
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Ana Paula de Melo Loureiro
• Grantee: Ana Paula de Melo Loureiro
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

There is a concern in identifying compounds involved in the development of deleterious processes. Markers of biological damage serve to evaluate the risk of disease development in cases of human exposure to xenobiotics in the environment and/or in the workplace. Among the possible markers, DNA adducts allow the identification of substances with genotoxic activity and the monitoring of human exposure to genotoxic agents. RNA adducts are beginning to be pointed as markers more sensitive than the DNA adducts. Besides this, RNA adducts are also able to trigger important biological effects. Our group has been focused in the study of mechanisms by which some substances exert its genotoxic effects. We have worked with xenobiotics like tetrahydrofuran (THF), a solvent carcinogenic to rodents and used widely in industries; a dinitrobromophenylazo dye used by textile industries, mutagenic in Salmonella tests, and discarded in industry effluents; and complex mixtures (solutions used in light sticks) searching the reactive substances present through the analysis of adduct formation with biomolecules. The role of oxidative stress in the toxicity of these agents must also be clarified. Quantitative studies comparing DNA lesions induced directly by the agent and indirectly by oxidative stress may lead to the development of different therapeutic strategies. The general objective of this project is to investigate the induction of DNA and RNA lesions by some xenobiotics, as well as to reveal mechanisms by which these toxic substances act. (AU)

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)

BROHEM, CARLA A.; MASSARO, RENATO R.; TIAGO, MANOELA; MARINHO, CAMILA E.; JASIULIONIS, MIRIAM G.; DE ALMEIDA, REBECA L.; RIVELLI, DIOGO P.; ALBUQUERQUE, RENATA C.; DE OLIVEIRA, TIAGO F.; DE MELO LOUREIRO, ANA P.; et al. Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death. PIGMENT CELL & MELANOMA RESEARCH, v. 25, n. 3, p. 354-369, MAY 2012. (08/58817-4, 06/50479-7, 09/54816-6)

DE OLIVEIRA, TIAGO FRANCO; MEDEIROS DA SILVA, AMANDA LUCILA; DE MOURA, RAFAELA ALVES; BAGATTINI, RAQUEL; FALCAO DE OLIVEIRA, ANTONIO ANAX; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE ARRUDA CAMPOS, IVAN PERSIO; BARRETTO, FABIANO PRADO; HENRIQUES BECHARA, ETELVINO JOSE; et al. Luminescent threat: toxicity of light stick attractors used in pelagic fishery. SCIENTIFIC REPORTS, v. 4, JUN 19 2014. (06/56530-4, 12/21636-8, 12/08616-8, 12/08617-4, 09/54816-6, 13/07937-8)