Abstract
CYP3A rapidly disappears in primary hepatocytes, although the primary cells are suitable for studies of the regulation of n CYP3A genes. In the present study, we found that Cyp3a mRNA could be expressed in the primary 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 CYP3A, was maintained at a level of 50% of the initial activity even after 5 days of culture, and the activity correlated with the expression level of Cyp3a mRNA in the primary hepatocytes from p53-knockout mice. The cells remained morphologically intact during 4 weeks. These results suggest that hepatocytes from p53-knockout mice are a useful tool for studies of the expression of Cyp3a.
