Effects of acute or chronic treatment of rats with N-2-fluorenylacetamide on its N-hydroxylation and on hemoproteins of hepatic microsomes.
Acute or chronic treatment of Sprague-Dawley rats with N-2-fluorenylacetamide (2-FAA) significantly increased the capacity of hepatic microsomes for N-hydroxylation of 2-FAA. The optimal increases, 11- and 16-fold, were measured in hepatic microsomes of male and female rats, respectively, 24 hr after a single intraperitoneal injection of 0.67 mmole 2-FAA/kg of body weight. The increases in 2-FAA N-hydroxylating activity were not paralleled by any appreciable changes in the content of cytochrome P-450. After oral intake of 2-FAA, small increases in the content of cytochrome b5 and of total heme were measured. Gel electrophoresis showed the presence of a new protein, staining for heme, in the MW region of 46,000 as soon as 24 hr after treatment of rats with at least 0.34 mmole 2-FAA/kg of body weight. The intensity of this protein band was enhanced by prolonged treatment of rats with 2-FAA, but was not paralleled by the extent of induction of N-hydroxylation of 2-FAA. This protein was induced in hepatic microsomes of rats both susceptible (male) and nonsusceptible (female) to hepatocarcinogenesis by 2-FAA. The data suggest that the 2-FAA-induced protein may not be a specific marker of early preneoplastic changes in rat liver.
D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D005260:Female; D006418:Heme / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D013997:Time Factors
D003580:Cytochromes; D006420:Hemeproteins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene