An early event associated with liver carcinogenesis involving loss of a polypeptide that binds carcinogen.

This report describes an early and direct action of oncogenic agents and its apparent consequences. Chemical carcinogen has been found to interact principally with a specific polypeptide in livers of normal rats. Short-term ingestion of carcinogen causes marked reductions in the concentrations of both the carcinogen:polypeptide complex and the polypeptide itself. This action and its consequences are unique in several ways. (a) Chemical carcinogen is directly involved in the event. (b) Three kinds of liver carcinogens act in this way: the aromatic amide, N-2-fluorenylacetamide (2-acetylaminofluorene); the aminoazo dye, 3'-methyl-4-dimethylaminoazobenzene; and the amino acid analog, ethionine. (c) The interaction of chemical carcinogen with a specific polypeptide is involved. (d) Both the carcinogen:polypeptide complex and the polypeptide itself undergo marked reductions in concentration during hepatocarcinogenesis by the three types of carcinogens. (e) The consequences of the interaction are sensitive indicators unusually early during liver carcinogenesis. (f) The target polypeptide has a molecular weight of 14,700, similar to those of known polypeptide growth regulators.