title: Insulin-Like Growth Factor-1-Mediated DNA Repair in Irradiated Salivary Glands Is Sirtuin-1 Dependent.
abstract: Ionizing radiation is one of the most common cancer treatments; however, the treatment leads to a wide range of debilitating side effects. In patients with head and neck cancer (HNC), the surrounding normal salivary gland is extremely sensitive to therapeutic radiation, and damage to this tissue results in various oral complications and decreased quality of life (QOL). In the current study, mice treated with targeted head and neck radiation showed a significant increase in double-stranded breaks (DSB) in the DNA of parotid salivary gland cells immediately after treatment, and this remained elevated 3 h posttreatment. In contrast, mice pretreated with insulin-like growth factor-1 (IGF-1) showed resolution of the same amount of initial DNA damage by 3 h posttreatment. At acute time points (30 min to 2 h), irradiated parotid glands had significantly decreased levels of the histone deactylase Sirtuin-1 (SirT-1) which has been previously shown to function in DNA repair. Pretreatment with IGF-1 increased SirT-1 protein levels and increased deacetylation of SirT-1 targets involved in DNA repair. Pharmacological inhibition of SirT-1 activity decreased the IGF-1-mediated resolution of DSB. These data suggest that IGF-1 promotes DNA repair in irradiated parotid glands through the maintenance and activation of SirT-1.
authors.affiliation: 1 Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Meyer
authors.affiliation: 1 Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Chibly
authors.affiliation: 1 Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA.
authors.forename: R
authors.initials: R
authors.lastname: Burd
authors.affiliation: 1 Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Limesand
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D010306:Parotid Gland / Q000378:metabolism / Q000528:radiation effects; D060888:Real-Time Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism / Q000528:radiation effects*; D056564:Sirtuin 1 / Q000502:physiology*; D014987:Xerostomia / Q000209:etiology
chemical_list: D007334:Insulin-Like Growth Factor I; D056564:Sirtuin 1
keywords: DNA repair; IGF-1; Sirtuin-1; radiation; salivary glands; xerostomia