Effects of sodium salts of phenobarbital and barbital on development of bladder tumors in male F344/NCr rats pretreated with either N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide or N-nitrosobutyl-4-hydroxybutylamine.

Promoting effects of sodium salts of phenobarbital (NaPB) and barbital (NaBB) on the development of bladder tumors were investigated in F344 male rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N-nitrosobutyl-4-hydroxybutylamine (BBN). To initiate with FANFT, rats were fed 0.2% FANFT mixed in diet for either 2 or 6 weeks and 2 weeks later were offered diet containing 1000 ppm of NaPB or NaBB. Rats were killed either at 52 or 68 weeks of age. To initiate with BBN, rats were given 0.05% BBN in drinking water for 4 weeks and beginning 1 day later were fed NaBB mixed in diet at 1000 ppm for up to 52 weeks. NaBB promoted bladder carcinogenesis initiated by either FANFT or BBN; the incidence and average number of simple or preneoplastic nodular (PN) hyperplasias, papillomas, and carcinomas per 10 cm of urothelium were significantly increased in the groups receiving NaBB following exposure to FANFT for 6 weeks (p less than 0.05) or BBN for 4 weeks (p less than 0.01). No such effect was seen in rats fed FANFT for only 2 weeks. NaPB also significantly increased (p less than 0.05) the frequency of preneoplastic PN hyperplasias but not the average number of papillomas and carcinomas per 10 cm of urothelium in rats fed FANFT for 6 weeks. NaBB was an effective promoter of bladder carcinogenesis under these experimental conditions, as expected from its known promoting effect on transitional epithelium of the renal pelvis, but NaPB in contrast did not affect the incidence or multiplicity of bladder papillomas or carcinomas under these conditions. NaPB could be considered a promoter for bladder urothelium only by the less rigorous criterion that it increased the frequency of preneoplastic PN hyperplasia.