title: Effect of sodium phenobarbital and sodium saccharin in AIN-76A diet on carcinogenesis initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and N,N-dibutylnitrosamine in male F344 rats.
abstract: Promoting activities of sodium phenobarbital (PB) and sodium saccharin (SS), incorporated in a semisynthetic diet (AIN-76A), on 2-stage carcinogenesis initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N,N-dibutylnitrosamine (DBN) in male F344 rats were investigated. For the first 4 weeks of the experiment, weanling male Fischer rats were fed Wayne diet containing 0.2% FANFT or drinking water containing 0.005% DBN. The control rats were given the basal diet and normal drinking water. Beginning at the fifth week, the rats were given the AIN-76A diet or this diet containing 0.05 or 0.15% PB or 5% SS. The experiment was terminated at the end of 100 weeks. PB significantly increased the incidence of transitional cell carcinoma of the bladder of the rats that had been treated with FANFT (P = 0.027). PB also increased the incidence of bladder carcinoma of the rats that had been treated with DBN, but the increase was not significant (P = 0.081). SS in the AIN-76A diet increased the incidence of bladder carcinoma in the rats which had been treated with FANFT or DBN, but the increase was not significant (P = 0.059 and 0.327, respectively). Both high and low doses of PB, but not SS, significantly increased the incidence of hepatocellular carcinoma in the rats that had been treated with DBN. None of the control rats that had been fed the basal diet or the basal diet containing low or high PB or 5% SS developed either bladder or liver carcinoma. These results demonstrate that PB promotes urinary bladder carcinogenesis of rats initiated with FANFT but not with DBN. In contrast to incorporation in commercial rat chows, SS incorporated in the AIN-76A diet is very weak in promoting bladder carcinogenesis. On the other hand, PB, but not SS, promotes hepatocarcinogenesis initiated with DBN. Neither PB nor SS promoted DBN-induced carcinogenesis of esophagus or forestomach.
mesh_terms: D000818:Animals; D004938:Esophageal Neoplasms / Q000139:chemically induced; D005200:FANFT; D006863:Hydrogen-Ion Concentration; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines / Q000633:toxicity*; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012439:Saccharin / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000139:chemically induced; D013844:Thiazoles; D013964:Thyroid Neoplasms / Q000139:chemically induced; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
chemical_list: D009602:Nitrosamines; D013844:Thiazoles; D005200:FANFT; C012279:dibutylnitrosamine; D012439:Saccharin; D010634:Phenobarbital