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Periodontal inflammation, oxidative and nitrative stress and DNA methylation

Grant number: 10/08180-0
Support type:Research Grants - Young Investigators Grants
Duration: May 01, 2011 - June 30, 2015
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Ana Paula de Souza
Grantee:Ana Paula de Souza
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Associated scholarship(s):11/09498-6 - Analysis of oxidative stress influence on DNA methylation profile, BP.PD


The infection-inflammation has been suggested as a factor involved in the etiology of several cancers, including oral cancer. Epidemiologic data support this hypothesis since connective tissue loss derived from chronic periodontitis has been associated with high risk to development of oral cancer (OR=4,57, 95% CI:2,25-9,30) and premalignant lesions of oral cavity (OR=1,55, 95% CI:1,06-2,27), but it is not associated with other benign lesions of oral tissues. The mechanisms by which inflammation would be predisposing risk for the development of tumors are not fully known. The production of oxygen-derived and nitrogen-derived reactive molecules during inflammation creates oxidative and nitrative stress in cells. These molecules can damage proteins, lipids and DNA. Among the changes promoted by these reactive molecules are the alterations in the pattern of DNA methylation in CpG dinucleotides of regions that control gene transcription. Methylation of genes that control events related to cell cycle, proliferation, cell division and apoptosis, i.e., tumor suppressor genes, raise the risk of developing cancer because it can reduce or silence the expression of these protective genes. Moreover, the loss of methylation of genes that promote mitosis increases the risk of developing tumors. The aim of this project is to investigate the effects of oxidative/nitrative stress derived from chronic inflammation on the transcription of enzymes that modify the chromatin epigenetic pattern and on epigenetic pattern of genes associated with oxidative/nitrative stress or with chronic inflammation of tissue cells that compose the oral mucosal. (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)
PLANELLO, ALINE C.; SINGHANIA, RAJAT; KRON, KEN J.; BAILEY, SWNEKE D.; ROULOIS, DAVID; LUPIEN, MATHIEU; PERES LINE, SERGIO R.; DE SOUZA, ANA PAULA; DE CARVALHO, DANIEL D. Pre-neoplastic epigenetic disruption enhancers in chronic inflammation of transcriptional. ONCOTARGET, v. 7, n. 13, p. 15772-15786, MAR 29 2016. Web of Science Citations: 4.
ANDIA, DENISE C.; PLANELLO, ALINE C.; PORTINHO, DANIELLE; DA SILVA, RODRIGO A.; SALMON, CRISTIANE R.; SALLUM, ENILSON A.; NOCITI JUNIOR, FRANCISCO H.; DE SOUZA, ANA P. DNA methylation analysis of SOCS1, SOCS3, and LINE-1 in microdissected gingival tissue. CLINICAL ORAL INVESTIGATIONS, v. 19, n. 9, p. 2337-2344, DEC 2015. Web of Science Citations: 3.
DE SOUZA, ANA PAULA; PLANELLO, ALINE CRISTIANE; MARQUES, MARCELO ROCHA; DE CARVALHO, DANIEL DINIZ; LINE, SERGIO ROBERTO PERES. High-throughput DNA analysis shows the importance of methylation in the control of immune inflammatory gene transcription in chronic periodontitis. CLINICAL EPIGENETICS, v. 6, AUG 12 2014. Web of Science Citations: 7.

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