title: The effect of radiation dose on mouse skeletal muscle remodeling.
abstract: BACKGROUND
  The purpose of this study was to determine the effect of two clinically relevant radiation doses on the susceptibility of mouse skeletal muscle to remodeling.
  
  
  METHODS
  Alterations in muscle morphology and regulatory signaling were examined in tibialis anterior and gastrocnemius muscles after radiation doses that differed in total biological effective dose (BED). Female C57BL/6 (8-wk) mice were randomly assigned to non-irradiated control, four fractionated doses of 4 Gy (4x4 Gy; BED 37 Gy), or a single 16 Gy dose (16 Gy; BED 100 Gy). Mice were sacrificed 2 weeks after the initial radiation exposure.
  
  
  RESULTS
  The 16 Gy, but not 4x4 Gy, decreased total muscle protein and RNA content. Related to muscle regeneration, both 16 Gy and 4x4 Gy increased the incidence of central nuclei containing myofibers, but only 16 Gy increased the extracellular matrix volume. However, only 4x4 Gy increased muscle 4-hydroxynonenal expression. While both 16 Gy and 4x4 Gy decreased IIB myofiber mean cross-sectional area (CSA), only 16 Gy decreased IIA myofiber CSA. 16 Gy increased the incidence of small diameter IIA and IIB myofibers, while 4x4 Gy only increased the incidence of small diameter IIB myofibers. Both treatments decreased the frequency and CSA of low succinate dehydrogenase activity (SDH) fibers. Only 16 Gy increased the incidence of small diameter myofibers having high SDH activity. Neither treatment altered muscle signaling related to protein turnover or oxidative metabolism.
  
  
  CONCLUSIONS
  Collectively, these results demonstrate that radiation dose differentially affects muscle remodeling, and these effects appear to be related to fiber type and oxidative metabolism.
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Hardee
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Puppa
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Fix
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
authors.forename: Kimbell L
authors.initials: KL
authors.lastname: Hetzler
authors.affiliation: Departments of Biomedical Engineering and Radiation Oncology, University of North Carolina - Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Bateman
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Carson
keywords: extracellular matrix; irradiation; oxidative metabolism; regeneration; skeletal muscle