Transformation-induced Alterations in the Regulation of Tyrosine Aminotransferase Expression in Fetal Rat Hepatocytes: Changes in Hormone Inducibility and the DNase-hypersensitive Site1

Regulation of expression of tyrosine aminotransferase (TAT) is exam ined in two cell lines (FRL) obtained by chemical transformation of cul tured fetal hepatocytes derived from 19-day rat fetuses (FL19). Steroid induction of TAT is unaffected by transformation, while the response to cyclic AMP is attenuated. Consequently a synergistic response elicited by the simultaneous exposure of normal fetal hepatocytes to the inducers is almost abolished in FRL cells. FL19 and FRL are similar with respect to the negative effect of insulin on steroid induction, which is a response restricted to prenatal liver. Detailed examination of chromatin reveals that the attenuated effect of cyclic AMP is consistent with the lack of the DNase I-hypersensitive site located at about the cyclic AMP response element of the TAT promoter. From the studies, we conclude that transformation results in the modification of some aspects of TAT regulation, while others have been retained, and reflects the fetal pattern which is observed in normal embryonic hepatocytes.