APPLICATION OF PRIMARY HEPATOCYTES FROM P53-KNOCKOUT MICE FOR STUDIESOF EXPRESSION OF CYP3A

CYP3A rapidly disappears in primacy hepatocytes, although the primary cells are suitable for studies of the regulation of CYP3A genes, in th e present study, we found that Cyp3a mRNA could be expressed in the pr imary hepatocytes from p53-knockout mice for at least 2 weeks when the cells were cultured in the presence of dexamethasone, Propoxycoumarin O-depropylase activity, which is known to be mainly catalyzed by CYP3 A, was maintained at a level of 50% of tire initial activity even afte r 5 days of culture, and the activity correlated with the expression l evel of Cyp3a mRNA in the primary hepatocytes from p53-knockout mice, The cells remained morphologically intact during 4 weeks, These result s suggest that hepatocytes from p53-knockout mice are a useful tool fo r studies of the expression of Cyp3a.