title: Modeling of chronic radiation-induced cystitis in mice.
abstract: OBJECTIVE
  Radiation cystitis (RC), a severe inflammatory bladder condition, develops as a side-effect of pelvic radiation therapy in cancer patients. There are currently no effective therapies to treat RC, in part due to the lack of preclinical model systems. In this study, we developed a mouse model for RC and used a small animal radiation research platform (SARRP) to simulate the targeted delivery of radiation as used with human patients.
  
  
  METHODS
  To induce RC, C3H mice received a single radiation dose of 20Gy delivered through two beams. Mice were subjected to weekly micturition measurements to assess changes in urinary frequency. At the end of the study, bladder tissues were processed for histology.
  
  
  RESULTS
  Radiation was well tolerated as no change in weight was observed in the weeks post treatment, and there was no hair loss at the irradiation sites. Starting at 17 weeks post treatment, micturition frequency was significantly higher in irradiated mice versus control animals. Pathological changes include fibrosis, inflammation, urothelial thinning and necrosis. At a site of severe insult, we observed telangiectasia, absence of Uroplakin-3 and E-cadherin relocalization.
  
  
  CONCLUSIONS
  We developed a RC model that mimics the human pathology and functional changes. Furthermore, radiation exposure attenuates the urothelial integrity long-term allowing for potential continuous irritability of the bladder wall from exposure to urine. Future studies will focus on the underlying molecular changes associated with this condition and investigate novel treatment strategies.
authors.affiliation: Beaumont Health System, Royal Oak, MI.
authors.forename: Bernadette M M
authors.initials: BM
authors.lastname: Zwaans
authors.affiliation: Beaumont Health System, Royal Oak, MI; Oakland University William Beaumont School of Medicine, Auburn Hills, MI.
authors.forename: Sarah
authors.initials: S
authors.lastname: Krueger
authors.affiliation: Beaumont Health System, Royal Oak, MI.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Bartolone
authors.affiliation: Beaumont Health System, Royal Oak, MI; Oakland University William Beaumont School of Medicine, Auburn Hills, MI; Lipella Pharmaceuticals, Pittsburgh, PA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.affiliation: Beaumont Health System, Royal Oak, MI; Oakland University William Beaumont School of Medicine, Auburn Hills, MI.
authors.forename: Brian
authors.initials: B
authors.lastname: Marples
authors.affiliation: Beaumont Health System, Royal Oak, MI; Oakland University William Beaumont School of Medicine, Auburn Hills, MI.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Lamb