METABOLISM OF 4-ACETAMIDOSTILBENE AND ITS N-HYDROXY DERIVATIVE

4-Acetamidostilbene (AAS) and the N-hydroxy derivative were rapidly excreted in faeces and urine following intraperitoneal administration to rats. The use of the faecal metabolic pathway was increased in rats pretreated with 4-aminostilbene compounds. The major urinary metabolites of AAS identified were 4′-hydroxy-AAS, and its deacetylated derivative, 3-hydroxy-AAS and N-hydroxy-AAS; the latter being the only carcinogenic compound. Additionally, a further unidentified metabolite was detected accounting for 10 to 15% of the urinary metabolites. Faecal metabolites of AAS were present mostly as free compounds, the major metabolite being 4′-hydroxy-AAS. The N-hydroxy-AAS metabolite excreted in urine from rats treated with AAS was mainly conjugated with glucosiduronic acid. The non-carcinogenic metabolites 4′-hydroxy-AAS and the deacetylated compound, 4′-hydroxy-AS, were preferentially excreted as sulphuric acid conjugates. The overall metabolism of N-hydroxy-AAS was similar to that of the parent amide, both with respect to the nature of the urinary metabolites and their relative concentrations. The major fraction of N-hydroxy-AAS was excreted as a glucosiduronic acid conjugate and the urinary levels of this conjugate were about 50%0 higher than in AAS-treated rats. These observations implicate N-hydroxylation as a metabolic activation process and it is postulated that the low response of liver to aminostilbene carcinogenesis reflects the efficiency of metabolic elimination from liver of the N-hydroxy metabolite in a stable conjugated form. This formation of a stable conjugate of the N-hydroxy metabolite coupled with the extensive use of the biliary metabolic pathway should allow wide tissue distribution of the carcinogen but other factors as yet undefined must also contribute to the high susceptibility of ear duct glands. © 1969, The British Empire Cancer Campaign for Research. All rights reserved.