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 unknown etiology. We sought to determine whether a cytotoxin is present in the urine of IC patients that could cause the epithelial damage seen 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 bladder cells. Results: The neutral red assay in T24 cells indicated the presence of a cytotoxin in 2 of 9 IC patient urine specimens. However, the more sensitive assay of cell proliferation (H-3-thymidine incorporation) in normal adult human bladder epithelial cells revealed antiproliferative activity in urine from 10 of 13 (77%) IC patients vs. 3 of 19 (16%) controls (two-way analysis of variance, p = .019). The antiproliferative 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, trypsin-sensitive factor(s). Conclusions: Because a denuded or damaged bladder epithelium is a central finding in IC, it is possible that the antiproliferative protein(s) contributes to the pathogenesis of this disease.