Organ-specific promoting effects of phenobarbital sodium and sodium saccharin in the induction of liver and urinary bladder tumors in male F344 rats.

Studied were conducted to determine whether initial treatment with N-2-fluorenylacetamide (2-FAA) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) followed by treatment with either phenobarbital sodium (PB) or sodium saccharin (SS) induced or enhanced liver and/or bladder tumorigenesis. Male inbred F344 rats were given 0.05% PB and 5.0% SS in the diet for 32 weeks after 4-week administration of 0.02% 2-FAA treatment and induced hyperplastic liver nodules after BBN treatment. The SS significantly enhanced induction of bladder hyperplasias, but not papilloma after BBN treatment, and induced bladder hyperplasias after 2-FAA treatment. However, PB had no effect on the bladder and SS had no effect on the liver after either 2-FAA or BBN treatment. The data indicate that although 2-FAA and BBN have tumor-initiating effects in the liver and urinary bladder, the tumor-promoting effects of PB and SS are organ-specific. The tumor-promoting effect of PB for the liver is relatively greater than that of SS for the urinary bladder.