Suppression of radiation-induced salivary gland dysfunction by IGF-1

Kirsten Limesand, Sherif Said, Steven M. Anderson

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: 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. Conclusions/Significance: 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.

Original languageEnglish (US)
Article numbere4663
JournalPLoS One
Volume4
Issue number3
DOIs
StatePublished - Mar 2 2009

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salivary glands
Salivary Glands
Insulin-Like Growth Factor I
Radiation
Apoptosis
apoptosis
neck
Neck
Xerostomia
acinar cells
Irradiation
Acinar Cells
irradiation
Head
quality of life
Therapeutics
preserves
mice
Quality of Life
Background Radiation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Suppression of radiation-induced salivary gland dysfunction by IGF-1. / Limesand, Kirsten; Said, Sherif; Anderson, Steven M.

In: PLoS One, Vol. 4, No. 3, e4663, 02.03.2009.

Research output: Contribution to journalArticle

Limesand, Kirsten ; Said, Sherif ; Anderson, Steven M. / Suppression of radiation-induced salivary gland dysfunction by IGF-1. In: PLoS One. 2009 ; Vol. 4, No. 3.
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