Expression of differentiated functions in hepatoma cell hybrids: alanine aminotransferase.

The expression of alanine aminotransferase (EC 2.6.1.2), an enzyme that is inducible in the liver, has been examined in somatic hybrid cells formed by crossing well-differentiated rat hepatoma cells with rat diploid epithelial cells, the former characterized by high activity and inducibility of the enzyme, and the latter by the absence of detectable activity. The hybrid cells that contain essentially complete chromosomal sets of the two parents show only very low activity and little inducibility. Among numerous "segregated" hybrid subclones, which have lost up to 40% of the chromosomes initially present, several show expression of intermediate levels of enzyme activity and very little inducibility, and two independent subclones are characterized by full re-expression of both baseline and inducible enzyme activity. The electrophoretic mobility of the enzyme from the latter hybrids, from the hepatoma parental cells, and from rat liver is identical. The absence of a correlation between total chromosome number of the hybrid cells and re-expression of alanine aminotransferase suggests that the loss of specific chromosomes is required for re-expression. In these hybrid cells, the re-expression of alanine aminotransferase baseline and inducibility is independent of that of tyrosine aminotransferase inducibility.