Decreased 3H-thymidine incorporation by human bladder epithelial cells following exposure to urine from interstitial cystitis patients.
OBJECTIVE
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.


METHODS
Evidence for a cytotoxin was sought using both a neutral red uptake viability assay in T24 bladder epithelial cells, and a 3H-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 (3H-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 Da), 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.
Keay
S
S
Department of Medicine, Department of veterans Affairs Medical Center, Baltimore, Maryland 21201, USA.
Zhang
C O
CO
Trifillis
A L
AL
Hise
M K
MK
Hebel
J R
JR
Jacobs
S C
SC
Warren
J W
JW
D000328:Adult; D002455:Cell Division; D018856:Cystitis, Interstitial / Q000652:urine*; D003603:Cytotoxins / Q000302:isolation & purification / Q000652:urine*; D004847:Epithelial Cells; D006801:Humans; D008970:Molecular Weight; D013936:Thymidine; D001743:Urinary Bladder / Q000166:cytology* / Q000378:metabolism*
D003603:Cytotoxins; D013936:Thymidine