Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins. I. Alpha-fetoprotein induction by ethionine.

The neoplastic cellular phenotype expresses many embryonic features. These features are believed to occur by derepression of embryonic genes during the carcinogenic process. A specific case is the ability of ethionine, a hepatocarcinogen, to induce an embryonic protein known as alpha-fetoprotein. A mechanism is proposed for this derepression process along with supporting evidence. It is hypothesized that the repressor protein for the alpha-fetoprotein gene must be modified (methylated) before it is functional and if for any reason this does not occur, alpha-fetoprotein will be produced. This simple theory can explain a variety of states of the liver cell in which alpha-fetoprotein is expressed namely i) fetal, ii) ethionine-treated, iii) neoplastic, and iv) tyrosinemic liver cells.