DEVELOPMENT OF DEXAMETHASONE-INDUCIBLE TYROSINE AMINOTRANSFERASE ACTIVITY IN WB-F344 RAT-LIVER EPITHELIAL STEMLIKE CELLS CULTURED IN THE PRESENCE OF SODIUM-BUTYRATE

Sodium butyrate acts as a differentiation-promoting agent for a wide variety of cell types, including some tumor cell lines. In this study, we examined the effects of sodium butyrate (SB) on the functional differentiation of cultured WB-F344 rat liver epithelial stemlike cells. Treatment of WB-F344 cells with 3.75 mM SE resulted in an inhibition of cellular proliferation, alterations to normal cellular morphology (increased cell size and decreased nuclear/cytoplasmic ratio), and significant increases in cellular protein synthesis. The SB-mediated changes in cell morphology, proliferative status, and protein catabolism were accompanied by development of dexamethasone-inducible tyrosine aminotransferase (TAT) enzyme activity. Culture of WB-F344 cells in growth medium containing SB and dexamethasone (DEX; 1 x 10(-6) M) resulted in greater than sevenfold increase in the basal TAT activity compared with control cultures. An additional sixfold increase in TAT activity was observed when cells cultured in medium containing SB and DEX were exposed to 1 x 10(-7) M DEX during the last 24 hours of culture. The DEX-inducible TAT activity developed by SE-treated WB-F344 cells responded to the modulating effects of insulin and L-tyrosine in a manner that closely resembled that reported for cultured hepatocytes and hepatoma cell lines. These studies show that treatment of WB-F344 rat liver epithelial stemlike cells with the differentiation-promoting agent SB in vitro leads to expression of the differentiation-specific hepatocyte enzyme TAT. (C) 1994 Wiley-Liss, Inc.