Carcinogenesis, Vol 18, 1485-1489, Copyright © 1997 by Oxford University Press
K Otori, Y Yano, N Takada, CC Lee, S Hayashi, S Otani and S Fukushima
Apoptosis is a morphologically and biochemically distinct form of cell
death which determines specific patterns of tissue size and shape and
balances cell proliferation. In the present study, the sequence of cellular
proliferative alterations in urinary bladder epithelium associated with
uracil-induced reversible urinary calculi was investigated in male F344
rats. Group 1 consisted of 45 rats, 6 weeks old at commencement of the
experiment, which were given a diet containing 3% uracil for 8 weeks and
were then returned to basal diet until week 20. Five rats were killed at
each of weeks 2, 4, 8, 9, 10, 11, 12, 14 and 20. Group 2 consisted of 15
rats which were given basal diet for 20 weeks. Five rats were killed at
each of weeks 0, 8 and 20. Microscopic, reversible papillomatosis, which
showed papillary projections of epithelial proliferation, was seen in the
urinary bladder of all rats in group 1 through week 8. No epithelial
lesions were apparent in any of rats in group 2. Anti-Le(y)(BM-1/JIMRO)-
positive areas of the urinary bladder epithelia were immunohistochemically
seen in all rats of group 1 at weeks 2-12. At week 9 the percentage of
anti-Le(y)-positive areas reached a maximum. Nick-end labeling stained
nuclei of cells in the urinary bladder epithelium were observed in all rats
of group 1 at weeks 4-14. At week 10 the labeling index was at a maximum.
Proliferating cell nuclear antigen (PCNA)- and cyclin D1-positive cells of
the urinary bladder epithelium were observed in group 1 at weeks 2, 4 and
8, however, at week 9 there were no PCNA- and cyclin D1-positive cells. In
urinary bladder papillomatosis the simultaneous existence of apoptotic
cells and proliferating cells was shown by double staining with anti-Le(y)
(BM-1/JIMRO) and for PCNA. At week 10 apoptosis, stained by BM-1 and
nick-end labeling, occurred extensively in regressing urinary bladder
papillomatosis. Agarose gel electrophoresis of DNA in regressing
papillomatosis at week 9 showed DNA fragmentation. Thus, these results
indicate that apoptosis occurs in the process of papilloma regression
following withdrawal of uracil treatment.
ARTICLES
Reversibility and apoptosis in rat urinary bladder papillomatosis induced by uracil
First Department of Pathology, Osaka City University Medical School, Osaka, Japan.
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