Cytokeratin and nonhistone protein antigenic changes in rat liver during azo dye but not hepatotoxin feeding.
Chromosomal proteins from rat liver have been assessed immunologically for changes in specific cytokeratins or primary tumor nonhistone proteins during treatment with an azo dye hepatocarcinogen (3'-methyl-4-dimethylaminoazobenzene), (3'-Me-DAB) or the hepatotoxin alpha-naphthyl-iso-thiocyanate (alpha-NIT). Fisher rats were fed laboratory diets supplemented with either agent and sacrificed sequentially at various intervals. Chromosomal proteins from these livers were electrophoresed in the presence of sodium dodecyl sulfate, transferred to nitrocellulose sheets and reacted with rabbit antisera to Novikoff hepatoma cytokeratin or 3'-Me-DAB induced primary hepatoma dehistonized chromatin. Livers from carcinogen-fed animals exhibited distinct, sequential changes in antigenic nonhistone proteins until the immunological specificity characteristic of the hepatoma was achieved concomitant with the induction of neoplasia. No antigenic changes were observed to occur in hepatotoxin-fed animals. The rat carcinoma-specific cytokeratin antigens p39 and p49 in Novikoff hepatoma were observed to appear as early as three weeks after the start of carcinogen feeding and were present maximally in 23 week livers with in situ carcinoma. These cytokeratins were not detected in alpha-NIT-fed animals. Our results support the concept that the carcinogenic process can be related to temporal changes in the expression of cell-specific cytokeratins in addition to nonhistone chromosomal proteins. Furthermore, these data suggest the expression of these antigenic species to not be the direct result of changes in liver structure and cellular composition associated with carcinogen toxicity; rather, neoplastic transformation is apparently required.
D015058:1-Naphthylisothiocyanate / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000032:analysis*; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D007633:Keratins / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000276:immunology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives*
D000941:Antigens; D002868:Chromosomal Proteins, Non-Histone; D008749:Methyldimethylaminoazobenzene; D015058:1-Naphthylisothiocyanate; D007633:Keratins; D004124:p-Dimethylaminoazobenzene