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EFFECT Of CHEMICAL AGENTS PRODUCED BY HUMAN ORAL SQUAMOUS CELL CARCINOMAS IN GLOBAL METHYLATION PROFILE OF DNA AND THE TP53 TUMOR SUPPRESSOR GENE OF NORMAL HUMAN KERATINOCYTES

Grant number: 12/19008-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2013
Effective date (End): July 31, 2014
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Rodrigo Augusto da Silva
Grantee:Louyse Vizotto Carvalho
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

The carcinogenic process is dependent on a multifactorial mechanism, characterized by genetic, epigenetic and phenotypic. These changes lead to malfunction of proto-oncogenes and tumor suppressor genes, mainly related to the control of genomic integrity, proliferation, differentiation and cell survival. Many of these changes involve the activation of signaling pathways or metabolic pathway, which promote cell growth and survival characteristics of the cell. In recent years, studies have shown early evidence of genomic alterations in histologically normal epithelia adjacent to oral carcinomas. The loss of cellular control mechanisms of epigenetic events may result in genomic instability, accumulation of DNA damage, uncontrolled cell proliferation and eventually tumor development. The encoded protein p53 is presented as a potent tumor suppressor, exerting central role in cellular response to DNA damage. The malfunction of this gene is involved in different tumor types, also found in more than half of cancers of head and neck. In this regard, recent evidence suggests the participation of epigenetic changes in the development of different types of neoplasms, particularly by hypo-or hyper protein. Thus, the objective of this project is to investigate the effect exerted by chemical factors produced by tumor cells on the profile of global DNA methylation and TP53 tumor suppressor gene in normal human keratinocytes.