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(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.
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(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.
Authors: C Kuperwasser; G D Hurlbut; F S Kittrell; E S Dickinson; R Laucirica; D Medina; S P Naber; D J Jerry Journal: Am J Pathol Date: 2000-12 Impact factor: 4.307
Authors: K Oda; H Arakawa; T Tanaka; K Matsuda; C Tanikawa; T Mori; H Nishimori; K Tamai; T Tokino; Y Nakamura; Y Taya Journal: Cell Date: 2000-09-15 Impact factor: 41.582
Authors: Arjan Vissink; James B Mitchell; Bruce J Baum; Kirsten H Limesand; Siri Beier Jensen; Philip C Fox; Linda S Elting; Johannes A Langendijk; Robert P Coppes; Mary E Reyland Journal: Int J Radiat Oncol Biol Phys Date: 2010-11-15 Impact factor: 7.038
Authors: Lucas T Woods; Jean M Camden; Josef M Batek; Michael J Petris; Laurie Erb; Gary A Weisman Journal: Am J Physiol Cell Physiol Date: 2012-08-08 Impact factor: 4.249
Authors: Bo Hai; Zhenhua Yang; Lei Shangguan; Yanqiu Zhao; Arthur Boyer; Fei Liu Journal: Int J Radiat Oncol Biol Phys Date: 2012-02-16 Impact factor: 7.038
Authors: Judith A E M Zecha; Judith E Raber-Durlacher; Raj G Nair; Joel B Epstein; Sharon Elad; Michael R Hamblin; Andrei Barasch; Cesar A Migliorati; Dan M J Milstein; Marie-Thérèse Genot; Liset Lansaat; Ron van der Brink; Josep Arnabat-Dominguez; Lisette van der Molen; Irene Jacobi; Judi van Diessen; Jan de Lange; Ludi E Smeele; Mark M Schubert; René-Jean Bensadoun Journal: Support Care Cancer Date: 2016-03-17 Impact factor: 3.603