An enhancing effect of the antihistaminic drug methapyrilene on rat liver carcinogenesis by previously administered N-2-fluorenylacetamide.

The effect on hepatocarcinogenesis of sequential administration of the antihistaminic drug methapyrilene (MP) or the typical liver tumor promoter, phenobarbital (PB), each given after the genotoxic liver carcinogen, N-2-fluorenylacetamide (FAA) was studied. An initial exposure to 0.02% of FAA in the diet for 8 weeks was used to produce hepatocellular altered foci. Rats maintained for an additional 24 weeks on basal diet developed a low incidence of liver neoplasms. MP at 500 and 1000 ppm in the diet for 24 weeks after FAA increased the frequency of altered foci at early stages and liver neoplasms later, as did PB. Neither MP nor PB alone produced neoplasms, but MP alone produced a significant incidence of altered foci. Therefore, the results provide evidence for a promoting action of MP, but additional effects may be involved in its carcinogenicity.