COMPARATIVE ADDUCT FORMATION OF 4-AMINOBIPHENYL AND 2-AMINOFLUORENE DERIVATIVES WITH MACROMOLECULES OF ISOLATED LIVER PARENCHYMAL-CELLS

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (7) , 2374-2381
Abstract
Isolated parenchymal cells of rat liver were used in a study of the metabolic activation of derivatives of the carcinogens 4-aminobiphenyl and 2-aminofluorene. The formation of adducts of these compounds with cellular RNA and protein was taken as evidence of their transformation to metabolites that are capable of spontaneous reaction with tissue macromolecules. The hydroxamic acid N-hydroxy-N-4-acetylaminobiphenyl was bound to RNA to a greater extent than the amino-, hydroxylamino-, nitroso-, nitro-, acetylamino- or azoxybiphenyl derivatives. RNA adducts of the hydroxamic acid retained little of the acetyl group. The structural requirements for binding and the nature of the bound derivatives are consistent with the activation of N-hydroxy-N-4-acetylaminobiphenyl by N .fwdarw. O acyltransfer. Approximately equal quantities of 4-nitrosobiphenyl and the hydroxamic acid were bound to protein, but less of the nitroso derivative was incorporated into RNA. Adduct formation of N-hydroxy-N-2-acetylaminofluorene with RNA occurred with retention of the acetyl group and was dependent on the concentration of sulfate in the media. Reaction of the fluorenyl derivative with RNA probably resulted from conjugation of the hydroxamic acid with sulfate.