Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis

Jennifer L. Avila, Oliver Grundmann, Randy M Burd, Kirsten Limesand

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Purpose: Radiotherapy for head-and-neck cancer causes adverse secondary side effects in the salivary glands and results in diminished quality of life for the patient. A previous in vivo study in parotid salivary glands demonstrated that targeted head-and-neck irradiation resulted in marked increases in phosphorylated p53 (serine18) and apoptosis, which was suppressed in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Methods and Materials: Transgenic and knockout mouse models were exposed to irradiation, and p53-mediated transcription, apoptosis, and salivary gland dysfunction were analyzed. Results: The proapoptotic p53 target genes PUMA and Bax were induced in parotid salivary glands of mice at early time points after therapeutic radiation. This dose-dependent induction requires expression of p53 because no radiation-induced expression of PUMA and Bax was observed in p53-/- mice. Radiation also induced apoptosis in the parotid gland in a dose-dependent manner, which was p53 dependent. Furthermore, expression of p53 was required for the acute and chronic loss of salivary function after irradiation. In contrast, apoptosis was not induced in p53-/- mice, and their salivary function was preserved after radiation exposure. Conclusions: Apoptosis in the salivary glands after therapeutic head-and-neck irradiation is mediated by p53 and corresponds to salivary gland dysfunction in vivo.

Original languageEnglish (US)
Pages (from-to)523-529
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume73
Issue number2
DOIs
Publication statusPublished - Feb 1 2009

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Keywords

  • Apoptosis
  • p53
  • Radiation
  • Salivary gland dysfunction
  • Salivary glands

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

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