Late changes in the normal mouse bladder after irradiation alone or in combination with cis‐DDP or cyclophosphamide, assessed by stereological analysis

Abstract

Stereological analysis has been performed to investigate the late changes in the normal mouse bladder one year after radiation alone (10–25 Gy) or radiation (10–15 Gy) combined with cyclophosphamide (CTX), 100 mg/kg, or cis‐diamminedichloroplatinum (II) (cis‐DDP), 6 mg/kg. A significant increase in total volume of urothelium was found in the group treated with CTX combined with radiation compared with the control. The total volume of connective tissue in the muscular layer in the groups which received X‐rays only showed a significant increase compared to the control. There also seemed to be an increase in the amount of connective tissue in muscular tissue, although this was not statistically significant, in the groups treated with CTX and irradiation compared with CTX alone. This indicates the importance of radiation in the development of late damage. Results from bladders treated with cis‐DDP alone or combined with radiation were statistically inconclusive due to the small number of animals in each group. The group treated with CTX and radiation (15 Gy) showed a significant decrease in the total volume of lamina propria, but no difference was found in the other treatment groups when comparing connective tissue, the muscular layer or the amount of vessels and capillaries with their corresponding control groups. Stereological analysis seems a feasible method to demonstrate late bladder tissue changes encountered after irradiation alone or combined with chemotherapy.

Radiation cystitis modeling: A comparative study of bladder fibrosis radio‐sensitivity in C57BL/6, C3H, and BALB/c mice

“…The change in bladder shape can be explained in C57BL/6 mice and BALB/c mice by increased fibrosis/total collagen or altered extracellular matrix composition, and was supported by voiding dysfunction. We did not observe any changes in fibrosis in the C3H strain, which is consistent with the findings of other studies (Lundbeck, Nielsen, et al, ; Lundbeck, Oussoren, et al, ). It is noteworthy that these previous studies did observe functional bladder changes in response to irradiation.…”

“…In this study, we show that radiation increases micturition frequency and decreases primary and average individual void size in C57BL/6 and, in a lesser extent, in BALB/c mice. While our methodology was not suitable to measure micturition patterns in C3H mice, previous studies have demonstrated altered micturition frequency in C3H mice after radiation (Lundbeck, Nielsen, & Stewart, ; Lundbeck, Oussoren, & Stewart, ; Zwaans et al, ). These changes are consistent with a functional decrease in bladder capacity.…”