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.
Department of Medicine, Department of veterans Affairs Medical Center, Baltimore, Maryland 21201, USA.
S
S
Keay
C O
CO
Zhang
A L
AL
Trifillis
M K
MK
Hise
J R
JR
Hebel
S C
SC
Jacobs
J W
JW
Warren
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