The gene expression sequence of radiated mucosa in an animal mucositis model

Abstract

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.

Figure 1

Typical mucositis curve following radiation of the hamster cheek pouch . Mucositis was induced with a single dose of radiation (35 Gy) administered on day 0. Irradiation specifically targeted the left buccal pouch mucosa using a lead shield to isolate it from the rest of the animal. Mucositis was scored on a scale ranging from 0 for normal, to 5 for severe ulceration using the following definitions: 0 = healthy pouch; 1 = erythema, but no mucosal erosion; 2 = severe erythema and vasodilation, superficial erosion may be present; 3 = ulcer formation at one or more sites with cumulative size of ulcers equal to or less than 25% of pouch surface area; 4 = ulceration with cumulative size equal to approximately 50% of pouch surface area; 5 = ulceration involving virtually all of pouch surface area.

Figure 2

Fluorogenic RT‐PCR measurement of heat shock protein 70 (▪), heat shock protein 90 (◆), cyclin A (s), p53 (×), and polδ (•) gene expression with respect to time following radiation.