@article {SOROF625, author = {SAM SOROF and EMILY M. YOUNG and REGINA Z. MCBRIDE and CAROL B. COFFEY and LEONA LUONGO}, title = {Increased Selectivity of Interaction between Fluorenylamine Carcinogens and Liver Proteins during Hepatocarcinogenesis}, volume = {5}, number = {6}, pages = {625--639}, year = {1969}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The continued ingestion of a fluorenylamine hepatocarcinogen by rats results in a marked change toward a highly selective interaction between the carcinogen and particular target liver proteins. Adult male rats were fed for 5 weeks a diet lacking (control) or containing the liver carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene, FAA). They were then given single doses of N-2-fluorenylacetamide-9-14C intragastrically and killed 48 hr later. The soluble liver proteins were resolved extensively by column electrophoresis. Control liver profiles displayed a diffuse distribution of fluorenyl-14C-proteins. In contrast, the profiles from rats previously fed the carcinogen displayed a highly localized concentration of bound 14C-labeled carcinogen at one or two weakly basic classes of proteins (fast h2 and/or slow h1). These regions contained about one-third of all the soluble fluorenyl-14C-proteins of liver, and represented a 3-4-fold increase over that in control profiles. Each of the two conjugates displayed a degree of electrophoretic homogeneity resembling that of a single macromolecule. The relative proportion of the two species varied considerably. The more anionic one (slow h1) was labile. The possibility that the specificity of protein binding in vivo resided in the activation of FAA by N-hydroxylation was examined by administration of the proximate carcinogen N-hydroxy-FAA-9-14C to rats likewise previously fed FAA. This premise was not supported by the finding of a similar h specificity of the distribution of radioactivity. In contrast to the h specificity of the preneoplastic livers of FAA-fed rats, unperfused primary liver tumors induced by FAA contained mostly soluble fluorenyl-14C-proteins which were weakly acidic (A proteins) and had a mobility similar to that of serum albumin.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/5/6/625}, eprint = {https://molpharm.aspetjournals.org/content/5/6/625.full.pdf}, journal = {Molecular Pharmacology} }