Intravesical treatment with mitomycin C (MMC) can result in a number of locally mediated urological adverse effects. The aim of this study was to use a porcine in vitro model to mimic the effects of intravesical MMC treatment and investigate how normal detrusor and urothelial function may be affected by treatment.

Porcine anterior bladder wall was incubated with MMC (2mg/mL) applied for 2hr to the luminal surface only. Following treatment, the release of urothelial mediators and contractile responses of isolated tissue strips were examined.

Isolated strips of urothelium/lamina propria from control bladders demonstrated a basal release of acetylcholine, ATP and PGE2, with increased release of ATP when tissues were stretched.  In tissues from MMC-pretreated bladders, the basal release of PGE2 was 33.6±8.6pM and it was significantly enhanced (2-fold, P<0.05) compared to the untreated control. In contrast, the stretch-induced release of ATP (13.1±4.6nM) was reduced by 80% (P<0.05) and the release of acetylcholine was not affected. In control tissues, detrusor muscle strips contracted to carbachol and these responses were inhibited by 26.8±12.3% (P<0.001) in tissues with an intact urothelium. Following MMC-pretreatment, detrusor contraction was depressed by 6.6±14.6% (P<0.05).  Also in tissues from MMC-pretreated bladders, the presence of an intact urothelium failed to inhibit detrusor contraction. The neurogenic detrusor muscle responses to electrical field stimulation increased with increasing stimulation frequency and the responses were depressed in MMC pretreated tissues compared to the control tissues with significant depression (P<0.05) at low stimulation frequencies of 1Hz and 5Hz.

MMC applied to the luminal surface of the bladder had significant effects on urothelial function, enhancing PGE2 release and abolishing the normal inhibitory effect of the urothelium on detrusor contraction.  MMC also depressed the contractile ability of the detrusor muscle (possibly reduced bladder compliance). These actions would tend to lead to bladder overactivity and reduced bladder volume, respectively, and may explain the increased frequency and urgency observed in patients following intravesical MMC treatment.