Restoration of radiation therapy‐induced salivary gland dysfunction by post therapy IGF1 administration

Abstract

Radiotherapy for head and neck cancer results in severe and chronic salivary gland dysfunction resulting in significant side effects including xerostomia and malnutrition. To address this problem we investigated the effect of IGF1 on the radiation response in normal tissue. Female mice were treated with targeted head and neck radiation and significant reductions in salivary function were confirmed 3 days after treatment. On days 4–8 after radiation, mice were divided into two groups with one group injected intravenously with IGF1 while the second group served as a vehicle injected control. Irradiated animals have 40–50% reductions in stimulated salivary flow rates. Mice receiving injections of IGF1 have increases in stimulated salivary flow rates 60–90 salivary flow rates that are not significantly different from unirradiated mice. Parotid tissue sections from irradiated animals show significant reductions in total amylase area when compared to unirradiated mice. Post‐therapeutic injections of IGF1 results in increased amylase‐positive acinar cell area on days 30–90. Post‐therapeutic IGF1 treatment restores salivary gland function through normalization of cell proliferation and improved expression of amylase. These findings could aid in the treatment of radiation‐induced salivary gland dysfunction in patients who have completed their anti‐cancer therapies. Supported in part by DE16096 and DE18888.