Radiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the United States each year. The ensuing salivary gland hypofunction results in significant morbidity and diminishes the effectiveness of anti-cancer therapies as well as the quality of life for these patients. Previous studies in a rat model have shown no correlation between induction of apoptosis in the salivary gland and either the immediate or chronic decrease in salivary function following γ-radiation treatment.

Methodology/Principal Finding

A significant level of apoptosis can be detected in the salivary glands of FVB mice following γ-radiation treatment of the head and neck and this apoptosis is suppressed in transgenic mice expressing an activated mutant of Akt (myr-Akt1). Importantly, this suppression of apoptosis in myr-Akt1 mice preserves salivary function, as measured by saliva output, three and thirty days after γ-radiation treatment. In order to translate these studies into a preclinal model we found that intravenous injection of IGF1 stimulated activation of endogenous Akt in the salivary glands in vivo. A single injection of IGF1 prior to exposure to γ-radiation diminishes salivary acinar cell apoptosis and completely preserves salivary gland function three and thirty days following irradiation.


These studies suggest that apoptosis of salivary acinar cells underlies salivary gland hypofunction occurring secondary to radiation of the head and neck region. Targeted delivery of IGF1 to the salivary gland of patients receiving head and neck irradiation may be useful in reducing or eliminating xerostomia and restoring quality of life to these patients.

Citation: Limesand KH, Said S, Anderson SM (2009) Suppression of Radiation-Induced Salivary Gland Dysfunction by IGF-1. PLoS ONE 4(3): e4663. doi:10.1371/journal.pone.0004663

Editor: Mikhail V. Blagosklonny, Ordway Research Institute, United States of America

Received: October 28, 2008; Accepted: January 16, 2009; Published: March 2, 2009

Copyright: © 2009 Limesand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported in part by the NIH grants PO1 DE12798 and R01 DE016354 to SMA, University of Colorado Cancer Center Translational Grant, and State of Colorado and University of Colorado Technology Transfer Office Bioscience Discovery Grant. KHL has received support from the Sjögren’s Syndrome Foundation (PN0101-097) and NIH (F32 DE 14315). KHL is the current recipient of a K22 award DE 16096. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.