A COMPARISON OF HEPATIC ENZYME-ACTIVITIES AND THEIR MODULATION BY DEXAMETHAZONE IN FRESHLY ISOLATED AND CULTURED-HEPATOCYTES AND IN THE DIFFERENTIATED HEPATOMA-CELL LINE, 2SFOU
Mj. Garle et Jr. Fry, A COMPARISON OF HEPATIC ENZYME-ACTIVITIES AND THEIR MODULATION BY DEXAMETHAZONE IN FRESHLY ISOLATED AND CULTURED-HEPATOCYTES AND IN THE DIFFERENTIATED HEPATOMA-CELL LINE, 2SFOU, ATLA. Alternatives to laboratory animals, 24(1), 1996, pp. 31-37
Rodent hepatocytes are mitotically inhibited and lose hepatospecific f
unctions over time in culture. In contrast, some differentiated hepato
ma cell lines express stable hepatospecific functions in culture, but
at much lower levels than those initially found in primary hepatocytes
. A number of hepatospecific functions were measured in freshly isolat
ed and cultured rat hepatocytes; these were compared to activities fou
nd in the differentiated Reuber hepatoma cell line, 2sFou. The effects
of dexamethazone on these activities were also investigated, since de
xamethazone is reported to enhance the expression of organotypic funct
ions. The P450-related activities (ethoxyresorufin-O-deethylase activi
ty and pentoxyresorufin-O-depentylase activity) and glucose-6-phosphat
ase activity declined in hepatocytes with increasing time in culture.
The same activities in 2sFou cells were similar to those in hepatocyte
s which had been cultured for 72 hours. Tyrosine amino transferase (TA
T) activity declined in hepatocyte cultures with time, but dexamethazo
ne (1 mu M) restored activity up to freshly isolated cell values. TAT
activity in hepatoma cells exceeded that in hepatocytes and was highly
inducible by dexamethazone. gamma-Glutamyl transpeptidase activity in
creased with culture time in hepatocytes and was also highly expressed
in 2sFou cells. In hepatocytes, the activity of a high affinity alcoh
ol dehydrogenase (ADH) declined with time in culture. In 2sFou cells,
there was evidence of a low affinity (extra-hepatic or fetal) form of
ADH, which was not evident in cultured hepatocytes.