EFFECT OF DELAY IN ADMINISTRATION OF 13-CIS-RETINOIC ACID ON THE INHIBITION OF URINARY-BLADDER CARCINOGENESIS IN THE RAT

Abstract

The effect of a delay in starting 13-cis-retinoic acid treatment on the inhibition of urinary bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine was studied in male Fischer 344 rats. Animals received a total p.o. [per os] dose of 1200, 1800 or 2400 mg N-butyl-N-(4-hydroxybutyl)nitrosamine over a period of 6 wk. At 1, 5 and 9 wk after the last N-butyl-N-(4-hydroxybutyl)nitrosamine intubation, animals were started on a diet supplemented with 13-cis-retinoic acid (240 mg/kg of laboratory chow) or after the 1st carcinogen intubation for histological evaluation of the bladder. Feeding of 13-cis-retinoic acid reduced the incidence, average number and severity of transitional cell carcinomas and hyperplasia and cellular atypia. Even a 9 wk delay in starting the retinoid feeding did not diminish the ability of 13-cis-retinoic acid to inhibit bladder carcinogenesis.