The Effect of Radiation Dose on Mouse Skeletal Muscle Remodeling

  • Justin P Hardee Department of Exercise Science, University of South Carolina, Columbia, SC, USA
  • Melissa J Puppa Department of Exercise Science, University of South Carolina, Columbia, SC, USA
  • Dennis K Fix Department of Exercise Science, University of South Carolina, Columbia, SC, USA
  • Song Gao Department of Exercise Science, University of South Carolina, Columbia, SC, USA
  • Kimbell L Hetzler Department of Exercise Science, University of South Carolina, Columbia, SC, USA
  • Ted A Bateman Departments of Biomedical Engineering and Radiation Oncology, University of North Carolina – Chapel Hill, Chapel Hill, NC, USA
  • James A Carson Department of Exercise Science, University of South Carolina, Columbia, SC, USA

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.  Materials and 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.  Conclusion: Collectively, these results demonstrate that radiation dose differentially affects muscle remodeling, and these affects appear related to fiber type and oxidative metabolism.
Published
2014-08-27
How to Cite
Hardee, J. P., Puppa, M. J., Fix, D. K., Gao, S., Hetzler, K. L., Bateman, T. A., & Carson, J. A. (2014). The Effect of Radiation Dose on Mouse Skeletal Muscle Remodeling. Radiology and Oncology, 48(3). Retrieved from https://www.radioloncol.com/index.php/ro/article/view/2129
Section
Experimental radiology