Metabolism of N-2-fluorenylacetamide in the hamster

Abstract

Summary In view of the increasing interest in the hamster as a species for toxicologic and pharmacologic work, especially in relation to carcinogenesis, the fate of N-2-fluorenylacetamide was examined in male and female hamsters by means of isotope and other microtechniques. Only a small part of the carbon-14 from a single dose of labeled compound appeared in the feces in 48 hours. The major portion was accounted for in the urine collected in the first 24 hours. The radioactivity of the liver and the kidneys was low, and about one-third and one-tenth of this activity, respectively, was firmly bound to protein. The urinary metabolites were 2.8 and 3.1% free, 79 and 83% as glucosiduronic acids, and 3.1 and 9.7% as sulfuric acid conjugates, respectively, in male and female hamsters. The free metabolites were chiefly N-(7-hydroxy-2-fluorenyl)acetamide, 2-amino-7-fluorenol, and N-2-fluorenylacetamide. Eliminated as glucosiduronic acids were mainly the 7-hydroxy, the 5-hydroxy-, and the N-hydroxy derivatives. The significant component in the sulfate ester fraction was the 7-hydroxy derivative, which was higher in the urine of female hamsters. Thus, hamsters appear to possess mainly the enzmye systems (1) for hydroxylation of N-2-fluorenylacetamide at the 7-position and on the nitrogen; (2) for conjugation of these products with glucuronic acid, and of the 7- hydroxy derivative with sulfuric acid; and (3) for deacetylation.