Add time:07/28/2019         Source:sciencedirect.com

As previously shown a 44- to 65-fold molar excess of acetanilide protected rats againts liver tumor induction by N-2-fluorenylacetamide. Analogs of acetanilide, the o-, m-, and p-isomers of acetotoluidides and aminobenzoic acids, were tested for inhibitory potential at a 44-fold molar excess dose on the carcinogenic effect of N-2-fluorenylacetamide. All 6 compounds prevented the death of male Fischer (F344) strain rats due to the toxic action of 300 ppm N-2-fluorenylacetamide. However, only m-acetotoluidide and m-aminobenzoic acid inhibited the carcinogenic effect of N-2-fluorenylacetamide, as did acetanilide. p-Aminobenzoic acid had a weak inhibitory effect since no hepatomas, but only hyperplastic nodules, were seen. o-Acetotoluidide was quite toxic by itself, producing enlarged livers with marked hydropic swelling and fatty changes, whereas o-aminobenzoic acid (anthranilic acid) did not lead to liver changes. Neither of the 2 o-substituted toluidine derivatives, nor p-acetotoluidide, affected liver tumor induction by N-2-fluorenylacetamide. These selective inhibitors of the toxicity and carcinogenicity of N-2-fluorenylacetamide provide new methods for the study of the underlying mechanisms.

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