Radiation Cystitis Modeling: a Comparative Study of Bladder Radiation‐Induced Fibrosis in Different Mouse Strains

Abstract

Introduction and ObjectiveRadiation cystitis (RC) is a severe side effect from radiation therapy that can occur in pelvic cancer survivors (e.g. cervical and prostate cancer) and results in a fibrotic bladder. However not all patients treated with pelvic radiation will develop RC. Different mouse strains can be used for exploring genetic variability with respect to human biology. We aimed to assess the fibrotic response of the bladder to radiation in various genetic mouse strains to determine if genetic background variation may explain differences in risk for patients developing RC after radiation treatment.MethodsFemale C57BL/6, C3H and Balb/c mice were given a single dose of 40 Gy irradiation using the Small Animal Radiation Research Platform (SARRP) to deliver a gamma‐irradiation to the bladder while limiting toxicity to neighboring tissue. Weekly micturition measurements were performed. Mice were sacrificed one‐year post irradiation and bladders were processed for histology. Fibrosis was determined using Mason's trichrome and Picrosirius Red stains.ResultsAll mice tolerated the radiation treatment well ‐ no changes in weight or behavior were noted. Micturition measurements were performed in C57BL/6 and Balb/c mice only, as C3H mice destroyed the filter paper. Increased number of voids, and decreased average and primary void size developed in both strains, though occurred earlier in the C57BL/6 strain. Hematuria developed in all strains. Mild to severe radiation‐induced fibrosis was visible in Balb/c and C57Bl/6 mice, with the highest degree of fibrosis in the latter. Fibermetrics analysis indicated higher number of collagen fibers in C57Bl/6 and Balb/c mice, but only Balb/c mice showed increased collagen fiber length and diameter. Ongoing studies will determine changes in specific collagen proteins using antibody specific fluorescent staining.ConclusionUsing SARRP, we can create bladder dysfunction in mice modeling symptoms of chronic human RC including hematuria, fibrosis, and micturition frequency. Radiation‐induced fibrosis in the bladder is strain dependent, suggesting that there may be a genetic predisposition to radiation sensitivity of the bladder. These results are essential in determining the right preclinical model for future RC studies and understanding which cancer patients are at risk for RC.Support or Funding InformationThis project was in part supported by the U Can‐Cer Vive Foundation, NIDDK K01 career development award DK114334 (BMMZ), NIDDK specialized center cooperative agreement award U54DK104310, and NIEHS predoctoral research award F31ES028594 (KW)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.