title: Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XIII. Mutational and non-mutational mechanisms as subsets of a more general mechanism. Part B--hereditary tyrosinemia.
abstract: In this mini-series three different examples of the etiology for the induction of alpha-fetoprotein and hepatocarcinogenesis have been chosen. The first paper describes the mechanism using the non-mutagen, ethionine. In this paper the mechanism is derived by virtue of a mutation that causes a deficiency in fumarylacetoacetate fumarylhydrolase activity with subsequent accumulation of fumarylacetoacetate that is an inhibitor of ATP: L-methionine S-adenosyltransferase. It is hypothesized that the chronically low levels of active methyl groups disallows base-pairing by the adenine moiety of S-adenosyl-L-methionine and the repressed conformation of the alpha-fetoprotein gene is altered and subsequent transcription takes place. The same or similar process occurs with the subset of genes (embryonically repressed) that as a special group of active genes gives embryonic features to a quasi-differentiated stem cell causing "dysdifferentiation" to a neoplastic state.
authors.forename: R L
authors.initials: RL
authors.lastname: Hancock
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics*; D005001:Ethionine / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics*; D009154:Mutation; D014443:Tyrosine / Q000097:blood*; D000509:alpha-Fetoproteins / Q000235:genetics*
chemical_list: D000509:alpha-Fetoproteins; D014443:Tyrosine; D005001:Ethionine