Metabolismo de espécies reativas em carcinoma espinocelular de cavidade oral

Abstract

Susceptibility for head and neck cancer is modulated by environmental and genetics factors. About 90% of these tumors are classified as head and neck squamous cells carcinoma which develops in the mucosal surface of the upper aero digestive tract. Alteration of the biotransformation mechanism of exogenous compounds can result in production of damaging substances and predispose to malignant cell development. Reactive oxygen species (ROS) are the result of biotransformation metabolism performed by antioxidant enzymes. Alteration of the expression or activity of these enzymes can lead to the increase of intra and extracellular ROS, which are able to promote oxidative damage in the cell, DNA mutation and disequilibrium of the cellular homeostasis which converge in pathological conditions such as cancer. Objectives: The present study evaluated the expression of genes involved in Phase II metabolism of exogenous compounds in oral squamous cells carcinoma (OSCC). Casuistic and Methods: Eight samples of OSCC and adjacent non tumor tissues were analyzed. The relative quantification of 84 genes involved in the antioxidant system was performed by quantitative real time Polymerase Chain Reaction in Real Time using the TaqMan Array Human Antioxidant Mechanisms (Applied Biosystems). Statistical analyses were performed using D'Agostino & Pearson omnibus normality test, One-sample T test, Wilcoxon signed rank test, Two-sample T Test and Mann-Whitney test. Results: Twenty-one genes presented differential expression in OSCC (P<0.05). Four genes exhibited high expression (ATOX1, PRDX4, PRNP and SOD2) and seventeen genes presented reduced expression (ALOX12, CAT, CSDE1, DHCR24, DUOX1, DUOX2, EPHX2, GLRX2, GPX3, GSR, GSTZ1, MGST3, PRDX1, OXR1, OXSR1, SOD1 and SOD3). The differential expressed genes are related to biological processes involved in carcinogenesis, such as inflammation, angiogenesis, apoptosis, genomic instability, invasion, survival and cell proliferation. Gene expression was not associated to clinic and pathologic parameters of the tumors. Conclusion: Genes encoding enzymes involved in the antioxidant metabolism of exogenous compounds present differential expression in OSCC. Alteration in the expression of these genes can modulate biological processes related to detoxification of toxic compound and predispose to malignant cell growth in the oral cavity.