N-hydroxy-2-fluorenylacetamide, an active intermediate of the mammary carcinogen N-hydroxy-2-fluorenylbenzenesulfonamide.
The mechanism of mammary carcinogenesis by N-hydroxy-2-FBS, a highly potent mammary carcinogen for the female rat by ip administration, has been investigated. Previous work in vivo indicating hydrolytic cleavage of the nitrogen-sulfur bond has been confirmed with the use of sonicates of mammary gland. One of the products of the hydrolysis was N-hydroxy-2-FA identified by its conversion to 2-FA. Since carcinogenicity tests by local application showed that N-hydroxy-2-FA was not carcinogenic for the mammary gland, desulfonylation of N-hydroxy-2-FBS by mammary gland does not account for mammary carcinogenesis. N-Hydroxy-2-FBS applied directly to the mammary gland was not carcinogenic and 2-nitrosofluorene, the product of the spontaneous decomposition of N-hydroxy-2-FBS, exhibited only weak carcinogenicity upon local application. In contrast, N-hydroxy-2-FAA, a urinary metabolite of N-hydroxy-2-FBS, was highly carcinogenic by local application and very likely mediates the action of N-hydroxy-2-FBS. A metabolic pathway for the conversion of N-hydroxy-2-FBS to N-hydroxy-2-FAA is presented. This pathway involves the intermediate formation, by mammary gland or liver, of N-hydroxy-2-FA. The site of the subsequent acetylation of the hydroxylamine is unknown at present although the mammary gland appears to be excluded.
D000818:Animals; D005260:Female; D005449:Fluorenes / Q000378:metabolism*; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000378:metabolism*; D000096926:Benzenesulfonamides
D005449:Fluorenes; D006881:Hydroxyacetylaminofluorene; D013449:Sulfonamides; C011282:N-hydroxy-2-fluorenylbenzenesulfonamide; D000096926:Benzenesulfonamides