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 Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2013
• End date: July 31, 2014
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Rodrigo Augusto da Silva
• Grantee: Louyse Vizotto Carvalho
• Host 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 the 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 pathways, 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 a central role in the 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 the 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 the TP53 tumor suppressor gene in normal human keratinocytes. (AU)