Carcinogenicity and Metabolism of Aromatic Amines in the Dog1

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Abstract
To determine the identity of the active carcinogenic metabolite in the urine of dogs given aromatic amines, we compared the metabolism of 1-naphthylamine and 2-naphthylamine in this species and found some of the following differences. 1) While 2-naphthylamine is metabolized to a unique diester [di(2-amino-1-naphthyl)phosphate], 1-naphthylamine is metabolized to a monophosphate ester of 2-amino-1-naphthol. 2) While 2-naphthylamine is metabolized exclusively to ortho-hydroxy conjugates, 1-naphthylamine is largely metabolized to para-hydroxy conjugates. 3) While both amines are N-hydroxylated, 2-naphthylamine is further oxidized to 2-nitrosonaphthalene. This further N-oxidative step does not appear to occur with the more stable N-1-naphthylhydroxylamine. The highly carcinogenic 4-aminobiphenyl is also metabolized to both the N-hydroxy and nitroso compounds. Experience has shown that the female beagle dog is the most suitable animal for testing bladder carcinogenic compounds.

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