Carcinogenicity and Metabolism of Aromatic Amines in the Dog

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...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1969-07, Vol.43 (1), p.263-269
Main Authors: Deichmann, William B., Radomski, Jack L.
Format: Article
Language:English
Subjects:
Amines - metabolism
Amines - toxicity
Amines - urine
Animals
Animals, Newborn
Bronchi
Carbon Isotopes
Carcinoma, Hepatocellular - chemically induced
Dogs
Female
Hydroxylamines
Hyperplasia - chemically induced
Liver Neoplasms
Lung Neoplasms - chemically induced
Lymphoma - chemically induced
Mucous Membrane
Naphthalenes - metabolism
Naphthalenes - toxicity
Naphthalenes - urine
Neoplasms, Experimental
Parity
Urinary Bladder
Urinary Bladder Neoplasms - chemically induced
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Summary: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.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/43.1.263