Application of primary hepatocytes from p53-knockout mice for studies of expression of Cyp3a

CYP3A rapidly disappears in primary hepatocytes, although the primary cells are suitable for studies of the regulation of 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.