Loss of alpha‐fetoprotein in rat hepatoma culture cells

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Abstract
The production of alpha‐fetoprotein (AFP) by cultured rat Morris hepatoma 7777 hepatoma cells was studied. Initially, in vitro, rat hepatoma tumor cells synthesized and released AFP into the culture medium. As subculturing progressed, however, their ability to produce AFP diminished. After 8 months of in vitro cultivation, a non‐AFP‐producing tumor cell line had not lost its tumorigenicity and produced a solid tumor when injected into two groups of Buffalo rats. New tumors derived from tissue culture cells have shown significantly lower levels of serum AFP than the in vivo tumor line. However, another subline of this hepatoma tissue culture (7777 Iowa) did not lose its ability to produce AFP after 1 year of in vitro culture. Electron microscopy demonstrated no morphological change when the two different lines (AFP‐producing and non‐AFP‐producing) were compared. Chromosomal analysis in these cell lines revealed that the non‐AFP‐producing line (7777 TC) had 42% cells with a diploid or near‐diploid complement whereas the AFP‐producing (7777 Iowa) line showed a greatly variable aneuploidy number with 45% of the cells near tetraploidy. The reason for the virtual loss of AFP production or the different response of this tumor cell in the rat hepatoma culture remains unknown. Our studies and others indicate that, though AFP is an oncofetal antigen and a gene product of tumor cells, the control mechanism of AFP production could be an epiphenomenon of tumor cell and not related to the control of tumor growth and differentiation.