THE FETAL SPECIFIC GENE CYP3A7 IS INDUCIBLE BY RIFAMPICIN IN ADULT HUMAN HEPATOCYTES IN PRIMARY CULTURE

We investigated by RNase protection the differential expression of CYP 3A4 and CYP3A7 mRNAs in fetal and adult human livers and in adult hepa tocytes in primary culture. Our results show that CYP3A7 is expressed in the liver of 8 of 9 adult Caucasians examined, at an average level of 1.7% of the level found in a fetal liver. CYP3A4 mRNA appeared to b e expressed in this fetal liver. In adult hepatocytes in primary cultu re, the constitutive level of CYP3A4 mRNA was low but detectable after 96 hours in untreated cells, but CYP3A7 mRNA remained undetectable. H owever, when the cells were treated for 48 hours with 25 mu M rifampic in, both CYP3A4 and CYP3A7 mRNAs were strongly induced in the 3 and in 2 of 3 cultures examined, respectively. Using an isoelectric focusing immunoblotting the two proteins were resolved. Protein CYP3A4 was del ectable in induced cells but CYP3A7 was not. These results show for th e first time that CYP3A7 and CYP3A4 mRNAs, but not the proteins, are c o-inducible by rifampicin in adult human hepatocytes in culture. (C) 1 996 Academic Press, Inc.