Exploring the Influence of Sex on the Development of Radiation-Induced Oral Mucositis

Oral mucositis is a significant side effect of chemotherapy, radiotherapy, or their combination in cancer patients. Current clinical management focuses primarily on symptom control, with few effective therapeutic agents. Understanding the factors influencing susceptibility to oral mucositis is essential for a comprehensive grasp of its pathophysiology. This study investigates sex as a biological variable in radiation-induced oral mucositis. Oral mucositis was induced via X-ray ionizing radiation using a fractionated dose of 8 Gy/d for 5 consecutive days, targeting only the head and neck area using male and female C57BL/6J mice aged 7 to 9 wk. Following sex-guided time points, we harvested tongues, stained with toluidine blue, and imaged to visualize mucosal damage. Histopathological analyses were performed using hematoxylin and eosin staining to assess mucositis severity and inflammatory infiltration. All irradiated groups showed a significant increase in mucositis severity versus controls, measured by the total number and area of ulcerative lesions as well as inflammatory cell infiltrate. Notably, there was a significant decrease in epithelial thickness in irradiated mice compared with nonirradiated controls, consistent with oral mucositis. Furthermore, female mice exhibited a greater area of ulcerative lesions and higher inflammatory cell infiltrate scores than males did. This study highlights the sexual dimorphism in the murine model of fractionated ionizing radiation-induced oral mucositis, demonstrating that female mice have an increased susceptibility to irradiation treatment.