The present experimental study was undertaken to clarify whether phenacetin and caffeine exert a cocarcinogenic and/or promoting effect on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-initiated urothelial carcinogenesis. BBN was initially administered to female Wistar rats by gavage in 3 consecutive fractionated doses of 100 mg/kg body weight each at 24-hour intervals. Phenacetin was continuously fed at a daily dose of 500 mg/kg body weight, and caffeine was given in the drinking water at a dose of 110 mg/kg body weight/day throughout the experiment. After an experimental period of 21 months the incidence of BBN-induced tumors in the urinary bladder (number of rats with a bladder tumor) had not increased following additional administration of phenacetin alone (47 %) or in combination with caffeine (48 %) compared with the control group, the animals of which received exclusively BBN (44%). However, there was a significant enhancement of a multifocal tumor development (number of rats with more than 1 tumor in the bladder), when additionally phenacetin was fed alone (44% of the tumor-bearing animals) or in combination with caffeine (47%) compared with the control rats treated with BBN alone which showed only solitary tumors. Similarly, the incidence of a multicentric tumor development had increased, although not significantly, following administration of phenacetin alone or simultaneously with caffeine for 15 months. Caffeine revealed no complete initiating carcinogenic potential for the resting as well as the regenerating bladder urothelium stimulated to proliferate by either a partial cystectomy or cyclophosphamide. Furthermore, no cocarcinogenic and/or promoting activity of caffeine on BBN-initiated bladder tumor development was observed. The data obtained suggest a slight promoting and/or cocarcinogenic effect of phenacetin on BBN-initiated bladder carcinogenesis as indicated by an enhancement of a multifocal tumor development.

Keywords:
Phenacetin, Caffeine, Lower urinary tract, Urothelial proliferation, Cocarcinogenic effect
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© 1987 S. Karger AG, Basel
1987
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