The Biosynthetic Preparation of C¹⁴-Labeled N-(1- and 3-Hydroxy-2-fluorenyl) acetamides, and Their Metabolism in Rats and Guinea Pigs

Abstract

The C¹⁴-labeled ortho-hydroxylated metabolites of the carcinogen N-2-fluorenylacetamide, N-(1- and 3-hydroxy-2-fluoren-9-C¹⁴-yl)acetamides, were prepared by biosynthesis in the rat. The metabolism of these compounds was studied in rats and guinea pigs after intraperitoneal injection. A larger percentage of a dose of either compound was excreted in the urine than in the feces. In rats and guinea pigs, 60 to 75 percent, and 90 percent, respectively, of the urinary radioactivity was in the form of glucuronides. The injected 1-hydroxy compound was excreted in the urine by rats as the 1-hydroxy, the 1,5-dihydroxy, and the 1,7-dihydroxy derivative, whereas guinea pigs eliminated mostly the 1,7-dihydroxy compound. About 69 percent of the urinary radioactivity was found to be the 3-hydroxy derivative: 8 percent as the 3,5- and 9 percent as the 3,7-dihydroxy derivative after administration of the 3-hydroxy compound to rats. Guinea-pig urine included 47 percent of the 3-hydroxy and 38 percent of the 3,7-dihydroxy derivative. Radioactivity from both injected compounds was present in all rat tissues examined. More isotope was tightly bound to the proteins of rat liver after injection of the 1-hydroxy derivative than after N-2-fluorenylacetamide, whereas the 3-hydroxy isomer gave lower levels. The specific activity of guinea-pig liver proteins was lowest after N-2-fluorenylacetamide, and somewhat higher after the 1- and 3-hydroxy compound. These results are discussed in relation to the species differences found between rats and guinea pigs, especially in regard to the apparent resistance of the latter species to carcinogenesis by N-2-fluorenylacetamide.