Interstitial cystitis antiproliferative factor (APF) as a cell-cycle modulator.
BACKGROUND
Interstitial cystitis (IC) is a chronic bladder disorder of unknown etiology. Antiproliferative factor (APF), a peptide found in the urine of IC patients, has previously been shown to decrease incorporation of thymidine by normal bladder epithelial cells. This study was performed to determine the effect of APF on the cell cycle of bladder epithelial cells so as to better understand its antiproliferative activity.


METHODS
Explant cultures from normal bladder biopsy specimens were exposed to APF or mock control. DNA cytometry was performed using an automated image analysis system. Cell cycle phase fractions were calculated from the DNA frequency distributions and compared by two-way analysis of variance (ANOVA).


RESULTS
APF exposure produced statistically significant increases in the proportion of tetraploid and hypertetraploid cells compared to mock control preparations, suggesting a G2 and/or M phase cell cycle block and the production of polyploidy.


CONCLUSIONS
APF has a specific effect on cell cycle distributions. The presence of a peptide with this activity may contribute to the pathogenesis of interstitial cystitis through disruption of normal urothelial proliferation and repair processes.
Rashid
Hani H
HH
Department of Urology, University of Rochester, Rochester, New York, USA. hani_rashid@urmc.rochester.edu
Reeder
Jay E
JE
O'Connell
Mary J
MJ
Zhang
Chen-Ou
CO
Messing
Edward M
EM
Keay
Susan K
SK
D000328:Adult; D000704:Analysis of Variance; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D018856:Cystitis, Interstitial / Q000473:pathology / Q000652:urine*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000652:urine; D006801:Humans; D008297:Male; D011003:Ploidies; D001743:Urinary Bladder / Q000473:pathology*
D006131:Growth Inhibitors