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.