J. Weisburger, P. H. Grantham, E. Weisburger
Jul 1, 1966
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Journal
Biochemical Pharmacology
Abstract
Abstract Because of its importance as a proximate carcinogen derived from N -2-fluorenylacetamide, the metabolic fate of N -2-fluorenylhydroxylamine was studied with isotopic techniques. In a 24-hr period after i.v. injection, adult female rats excreted 51 and 9.7 per cent of the dose in urine and feces, males 45 and 3.7 per cent. Liver and kidneys had 9.6 and 0.5 per cent (males), 8.3 and 0.4 per cent (females); liver and kidney proteins had 210 and 118 mμmoles/g (males), 137 and 118 mμmoles/g (females). The urinary metabolites in male rats consisted of sulfuric acid esters, glucosiduronic acids, and unconjugated compounds in decreasing order of magnitude; with females more glucosiduronic acids were found. The metabolites identified were the acetylated derivatives N -hydroxy- N -2-fluorenylacetamide and 3-, 5-, and 7-hydroxy- N -2-fluorenyl-acetamide, and also 2-amino-7-nuorenol, present in differing amounts in males and females. After zero 6 and 24 hr, increasing amounts of isotope were bound to serum proteins. At 24 hr, erthyrocytes were extensively labeled. Thus, highly reactive N -2-fluorenylhydroxylamine, as evidenced by tissue and serum binding, underwent acetylation followed by the metabolic transformation characteristic of the product, N -hydroxy- N -2-fluorenylacetamide. An isomerization of the hydroxylamine and a subsequent acetylation may also have occurred.