DECREASED H-3 THYMIDINE INCORPORATION BY HUMAN BLADDER EPITHELIAL-CELLS FOLLOWING EXPOSURE TO URINE FROM INTERSTITIAL CYSTITIS PATIENTS

Purpose: Interstitial cystitis (IC) is a chronic bladder disease of un known etiology. We sought to determine whether a cytotoxin is present in the urine of IC patients that could cause the epithelial damage see n in this disease. Materials and Methods: Evidence for a cytotoxin was sought using both a neutral red uptake viability assay in T24 bladder epithelial cells, and a H-3-thymidine incorporation assay in primary normal adult bladder epithelial cells and FHS 738 Bl human fetal bladd er cells. Results: The neutral red assay in T24 cells indicated the pr esence of a cytotoxin in 2 of 9 IC patient urine specimens. However, t he more sensitive assay of cell proliferation (H-3-thymidine incorpora tion) in normal adult human bladder epithelial cells revealed antiprol iferative activity in urine from 10 of 13 (77%) IC patients vs. 3 of 1 9 (16%) controls (two-way analysis of variance, p = .019). The antipro liferative activity of IC urine specimens was confirmed using FHS 738 Bl human fetal bladder cells. The antiproliferative urinary substance( s) appeared to be a low molecular weight (<10,000 Dal, heat stable, tr ypsin-sensitive factor(s). Conclusions: Because a denuded or damaged b ladder epithelium is a central finding in IC, it is possible that the antiproliferative protein(s) contributes to the pathogenesis of this d isease.