Correlation between iNOS, nitrate and nitrite and O6-methylguanina-DNA-methyltransferase in colorectal cancer

• Grant number: 08/01240-7
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2008
• End date: June 30, 2010
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Renata de Almeida Coudry
• Grantee: Renata de Almeida Coudry
• Host Institution: Hospital A C Camargo. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Colorectal carcinoma (CRC) is one of the most common human malignancies in the world. In addition to hereditary components, known risk factors for CRC are related to lifestyle and environment such as smoking and a Western diet (high meat and low fruit and vegetable intake). Individuals with a high intake of red and processed meat have a 20% elevated risk of CRC. Meat is source of several known mutagens including N-nitrosos compounds, heterocyclic amines and polycyclic aromatic hydrocarbons. Alkylating agents such as N-nitrosos compounds can modify cellular DNA and induce mutation and cancer. Among DNA adducts generated by these compounds, O6 methylguanine is one the major products and has the potential to induce cancer. To prevent such harmful outcome, organisms have a specific DNA repair enzyme, O6- Methylguanine-DNA Methyltransferase, which transfers methyl groups from both O6 methylguanine and O4 methylthymine moieties in alkylated DNA to its own molecule, thereby repairing the DNA lesions. The aim of the present study is to correlate N-nitrosos compounds with the DNA repair protein, O6- methylguanine-DNA methyltransferase, in colorectal cancer. We also want to study the role of inactivation of O6- Methylguanine-DNA Methyltransferase gene by methylation in those tumors. (AU)