RESUMO
Oral mucositis is a common, dose-limiting, acute toxicity of radiation therapy administered for the treatment of cancers of the head and neck. Accumulating data would suggest that the pathogenesis of mucositis is complex and involves the sequential interaction of all cell types of the oral mucosa, as well as a number of cytokines and elements of the oral environment. While a number of studies have reported on gene expression of particular cell types in response to radiation, the overall response of irradiated mucosa has only been evaluated in a limited way. The present study was undertaken to evaluate the expression of a target group of genes using RNA quantification assays and, more broadly, to assess patterns of mucosal gene expression using DNA microarray hybridization. Our results demonstrate the sequential upregulation of a series of genes that, when taken collectively, suggest an intricate functional interaction.
Assuntos
Mucosa Bucal/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos , Lesões Experimentais por Radiação/genética , Estomatite/genética , Animais , Cricetinae , DNA Polimerase III/genética , Modelos Animais de Doenças , Expressão Gênica/efeitos da radiação , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP90/genética , Masculino , Mesocricetus , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Lesões Experimentais por Radiação/fisiopatologia , Estomatite/fisiopatologia , Fator de Necrose Tumoral alfa/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Oral ulcerative mucositis is a common toxicity associated with drug and radiation therapy for cancer. It impacts on quality of life and economic outcomes, as well as morbidity and mortality. Mucositis is often associated with dose limitations for chemotherapy or is a cause for dose interruption for radiation. The complexity of mucositis as a biological process has only been recently appreciated. It has been suggested that the condition represents a sequential interaction of oral mucosal cells and tissues, pro-inflammatory cytokines and local factors such as saliva and the oral microbiota. The recognition that the pathophysiology of mucositis is a multifactorial process was partially suggested by the observation that interleukin-11 (IL-11), a pleotropic cytokine, favorably altered the course of chemotherapy-induced mucositis in an animal model. In the current study, we evaluated a series of biologic and morphologic outcomes to determine their roles and sequence in the development of experimental radiation-induced mucositis and to evaluate the effects of IL-11 in attenuating them. Our results suggest that IL-11 favorably modulates acute radiation-induced mucositis by attenuating pro-inflammatory cytokine expression. Data are also presented which help define the pathobiological sequence of mucositis.
