Organ-Specific Promoting Effects of Phenobarbital Sodium and Sodium Saccharin in the Induction of Liver and Urinary Bladder Tumors in Male F344 Rats23

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Abstract
Studies 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 or 0.01 % BBN. PB significantly enhanced hepatocarcinogenesis after 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.

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