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

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 (serine{sup 18}) 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 dysfunctionmore » in vivo.« less

Authors:
 [1]; ;  [2];  [1];  [3]
  1. Department of Physiological Sciences, University of Arizona, Tucson, AZ (United States)
  2. Department of Nutritional Sciences, University of Arizona, Tucson, AZ (United States)
  3. (United States), E-mail: limesank@u.arizona.edu
Publication Date:
OSTI Identifier:
21172597
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 73; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2008.09.036; PII: S0360-3016(08)03536-0; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; APOPTOSIS; HEAD; IN VIVO; IRRADIATION; KNOCK-OUT REACTIONS; NECK; NEOPLASMS; RADIATION DOSES; RADIOTHERAPY; SALIVARY GLANDS; SIDE EFFECTS; TRANSCRIPTION; TRANSGENIC MICE

Citation Formats

Avila, Jennifer L., Grundmann, Oliver, Burd, Randy, Limesand, Kirsten H., and Department of Nutritional Sciences, University of Arizona, Tucson, AZ. Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis. United States: N. p., 2009. Web. doi:10.1016/j.ijrobp.2008.09.036.
Avila, Jennifer L., Grundmann, Oliver, Burd, Randy, Limesand, Kirsten H., & Department of Nutritional Sciences, University of Arizona, Tucson, AZ. Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis. United States. doi:10.1016/j.ijrobp.2008.09.036.
Avila, Jennifer L., Grundmann, Oliver, Burd, Randy, Limesand, Kirsten H., and Department of Nutritional Sciences, University of Arizona, Tucson, AZ. Sun . "Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis". United States. doi:10.1016/j.ijrobp.2008.09.036.
@article{osti_21172597,
title = {Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis},
author = {Avila, Jennifer L. and Grundmann, Oliver and Burd, Randy and Limesand, Kirsten H. and Department of Nutritional Sciences, University of Arizona, Tucson, AZ},
abstractNote = {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 (serine{sup 18}) 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.},
doi = {10.1016/j.ijrobp.2008.09.036},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 73,
place = {United States},
year = {2009},
month = {2}
}