Neoplastic conversion in rat liver by the antihistamine methapyrilene demonstrated by a sequential syncarcinogenic...

A study was performed to determine whether the enhancing effect of the antihistamine methapyrilene (MP) in rat liver carcinogenesis represents promotion or syncarcinogenesis . The effect on hepatocarcinogenicity induced by N-2-fluorenylacetamide (FAA) of sequential administration of MP given either before or after FAA was studied in comparison with diethylnitrosamine (DEN) also given either before or after FAA. MP in either sequence with FAA enhanced liver carcinogenicity as did DEN. Moreover, MP by itself induced liver altered foci, albeit at a high dose for a prolonged interval. A single liver neoplasm occurred with exposure to MP alone. These findings suggest that MP produces neoplastic conversion of liver cells which can be summated with the genotoxic effect of FAA to produce syncarcinogenesis .