Transformation of human bronchial epithelial cells by benzo[a]pyrene: metabolic redox processes and DNA methylation / demethylation

• Grant number: 12/21636-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2013
• End date: December 31, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Ana Paula de Melo Loureiro
• Grantee: Tiago Franco de Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Lung cancer is considered a serious health problem worldwide. Its high mortality rate is a direct reflex of the difficulty of early diagnosis and the refractivity of the advanced stages of this malignancy to conventional therapy. Thus, major advances in treatment may arise from a better understanding of the molecular origins of the disease and cellular changes underlying the transformation and proliferation of precancerous cells. One of the most recent promising targets for therapy is the metabolism of malignancies, since it is altered relative to normal non-proliferating cells. The objective of this project is to determine whether metabolic changes induced by the known carcinogen benzo[a]pyrene in human bronchial epithelial cells (BEAS-2B) contributes to epigenetic alterations leading to gene silencing and malignant transformation. Concomitantly, lesions will be evaluated in the DNA of cells in order to check the contribution of the genotoxic pathway for cellular transformation under the conditions used. Although there are published data showing that inactivating mutations of enzymes of the Krebs cycle lead to changes in the levels of 5-mdC and 5-hmdC in DNA, there are no studies that show a relationship between these changes from the action of a carcinogen. Besides contributing to the area with the elucidation of a possible new route of carcinogenic action of benzo[a]pyrene, which may be common to many carcinogens, the experimental design of this project will enable the creation of a base of laboratorial methods that can be used by different groups interested in the relationship between metabolic changes and the development of diseases.

Scientific publications

(5)

(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)

DE OLIVEIRA, ANTONIO ANAX F.; DE OLIVEIRA, TIAGO F.; BOBADILLA, LARISSA L.; GARCIA, CAMILA C. M.; BERRA, CAROLINA MARIA; DE SOUZA-PINTO, NADJA C.; MEDEIROS, MARISA H. G.; DI MASCIO, PAOLO; ZATZ, ROBERTO; LOUREIRO, ANA PAULA DE M.. Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory. SCIENTIFIC REPORTS, v. 7, JAN 12 2017. (12/08617-4, 13/11747-0, 12/21636-8)

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)

DE OLIVEIRA, TIAGO FRANCO; FELCAO DE OLIVEIRA, ANTONIO ANAX; LEMOS, MIRIAM; VERAS, MARIANA; NASCIMENTO SALDIVA, PAULO HILARIO; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE MELO LOUREIRO, ANA PAULA. Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 147, MAY 2019. (13/07937-8, 11/09891-0, 12/08617-4, 12/21636-8, 12/08616-8, 12/22190-3)

FALCAO DE OLIVEIRA, ANTONIO ANAX; DE OLIVEIRA, TIAGO FRANCO; DIAS, MICHELLE FRANCINI; GENNARI MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; VERAS, MARIANA; LEMOS, MIRIAM; MARCOURAKIS, TANIA; NASCIMENTO SALDIVA, PAULO HILARIO; MELO LOUREIRO, ANA PAULA. Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from SAo Paulo city, Brazil. PARTICLE AND FIBRE TOXICOLOGY, v. 15, OCT 19 2018. (12/08617-4, 12/08616-8, 11/09891-0, 12/22190-3, 12/21636-8, 13/07937-8)

DE OLIVEIRA, TIAGO FRANCO; FELCAO DE OLIVEIRA, ANTONIO ANAX; LEMOS, MIRIAM; VERAS, MARIANA; NASCIMENTO SALDIVA, PAULO HILARIO; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE MELO LOUREIRO, ANA PAULA. Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, v. N/A, n. 147, p. 19-pg., 2019-05-01. (13/07937-8, 12/22190-3, 12/08616-8, 11/09891-0, 12/08617-4, 12/21636-8)