Induction of microsomal N-hydroxylation of N-2-fluorenylacetamide in rat liver

Autor: Andrew L. Glasebrook, Danuta Malejka-Giganti, Helmut R. Gutmann, Robert C. McIver
Rok vydání: 1978
Předmět:
Zdroj: Biochemical Pharmacology. 27:61-69
ISSN: 0006-2952
DOI: 10.1016/0006-2952(78)90257-5
Popis: Single or multiple injections of N -2-fluorenyl-acetamide (2-FAA) to Sprague-Dawley rats increased N -hydroxylation of 2-FAA by hepatic microsomes 3- to 12-fold without changing the content of microsomal hemoprotein (cytochrome P-450 or P 1 -450) measured either by carbon monoxide difference spectra, by gel electrophoresis of microsomal preparations or by formation of the ethyl isocyanide cytochrome P 1 -450 complex. Carbon monoxide inhibited N -hydroxylation of 2-FAA by hepatic microsomes of 2-FAA-treated rats. Inhibition by carbon monoxide indicated that either cytochrome P-450 or P 1 -450 is the terminal oxidase in N -hydroxylation by microsomes of 2-FAA-treated rats. Unlike pretreatment of rats with phenobarbital or 3-methylcholanthrene, pretreatment with 2-FAA did not appear to induce the synthesis of microsomal hemoprotein. The activities of NADPH-cytochrome c reductase, NADPH-cytochrome P-450 reductase and of amine oxidase in microsomes of 2-FAA-treated rats were not increased and thus did not account for the stimulation of N -hydroxylation. The induction, by 2-FAA, of a heretofore unknown electron carrier associated with the hepatic mixed-function oxidase is postulated and under investigation.
Databáze: OpenAIRE