[Effect of liarozole on the cell proliferation activity in the rat urinary bladder epithelium induced by N-butyl-N-(4-hydroxybutyl) nitrosamine].
OBJECTIVE
Recently, the chemopreventive effects of various drugs on N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN) induced rat urinary bladder carcinogenesis have been reported. The aim of this study was to evaluate the effect of liarozole, an antitumor agent that inhibits the metabolism of retinoids, on the initial stage of BBN induced rat urinary bladder carcinogenesis.


METHODS
Seven-week-old, male Wistar rats were used. The rats were divided into four groups. All groups except control were allowed free access to the drinking water containing 0.05% BBN. Groups Lz40 (n = 5) and Lz80 (n = 5) were administered the liarozole solution, twice daily by gavage (40 mg/kg/day and 80 mg/kg/day, respectively). Group BBN (n = 5) was given no liarozole. The control group (n = 4) received no carcinogen. At 9 weeks after the start of the experiment, all rats were killed by ether anesthesia and their urinary bladders were taken for evaluation. The urinary bladders were fixed in 10% buffered formalin, embedded in paraffin, sectioned, and immunohistochemical staining using anti-proliferative cell nuclear antigen (PCNA) antibody was performed by the avidin-biotin-peroxidase complex (ABC) method. We calculated the PCNA positive rate and compared among the four groups.


RESULTS
The PCNA positive rate of group BBN was 23.5 +/- 3.7%. Compared with group BBN, the PCNA positive rate of groups Lz40 and Lz80 were statistically less (16.4 +/- 4.3% and 9.8 +/- 2.6%, respectively). Furthermore, the PCNA positive rate of group Lz80 was statistically less than that of group Lz40.


CONCLUSIONS
The results indicate that liarozole may inhibit the activity of cell proliferation in the initial stage of BBN-induced rat urinary bladder carcinogenesis and may be dose-dependent.
Nagae
H
H
Department of Urology, Hamamatsu University School of Medicine.
Otawara
Y
Y
Suzuki
K
K
Fujita
K
K
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002085:Butylhydroxybutylnitrosamine; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000166:cytology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology*
D018931:Antineoplastic Agents, Hormonal; D007093:Imidazoles; D002085:Butylhydroxybutylnitrosamine; C061121:liarozole