The Metabolism of Aromatic Amines in Relation to Carcinogenesis

SOME years ago, in connection with work on the metabolism of carcinogenic azo compounds, the method of excretion by the rat of a number of aromatic amines was studied. A preliminary account of some of this work was given at a meeting of the Biochemical Society (Elson, Goulden and Warren, 1946). Many aromatic amines are excreted as ethereal sulphates of amino phenols, and one of the aims of this work was to investigate the effects of the amines on sulphur metabolism as had been done previously for a series of aromatic hydrocarbons (Elson, Goulden and Warren, 1945). The investigation was concerned therefore mainly with determining changes in the daily excretion of ethereal sulphate, inorganic sulphate, neutral sulphur and of glucuronic acid in the urine following administration of the aromatic amines. It was hoped eventually to investigate more completely the metabolism of individual amines and to characterise definitely their metabolites, but this extended investigation has not been possible in most cases. The subsequent discovery of of the carcinogenic action in rats of a number of the amines, e.g. aminostilbenes (Haddow, Harris, Kon and Roe, 1948; Elson, 1952a), 4-dimethylamino-diphenyl (Miller, Miller, Sandin and Brown, 1949), benzidine (Spitz, Maguigan and Dobriner, 1950), and, in particular, 4-amino-diphenyl and 3: 2'-dimethyl-4-aminodiphenyl by Walpole, Williams and Roberts (1952) and their suggestion that ortho hydroxyamines may be direct-acting carcinogens, has suggested the possibility of an interesting relationship between our findings for the metabolism of these aromatic amines and their carcinogenic action. The purpose of the present paper therefore is to describe in more detail the results of our metabolism studies and to discuss their possible significance in relation to carcinogenesis.