THEORETICAL MECHANISMS FOR SYNTHESIS OF CARCINOGEN-INDUCED EMBRYONIC PROTEINS .13. MUTATIONAL AND NON-MUTATIONAL MECHANISMS AS SUBSETS OF A MORE GENERAL MECHANISM .B. HEREDITARY TYROSINEMIA

Abstract

In this mini-series, 3 different examples of the etiology for the induction of .alpha.-fetoprotein and hepatocarcinogenesis were chosen. 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, an inhibitor of ATP:L-methionine-S-adenosyltransferase. It is hypothesized that the chronically low levels of active methyl groups disallow 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.