Localization of Cytochrome P–450 Gene Expression in Normal and Diseased Human Liver By In Situ Hybridization of Wax–Embedded Archival Material

Abstract

The localization of the expression of several cytochrome P–450 genes in normal and diseased human liver was investigated by in situ hybridization of formalin–fixed, paraffin wax-embedded archival tissue samples with ³⁵S–labeled antisense RNA probes. The results demonstrated that genes coding for members of the cytochrome P–450 3A subfamily (CYP3A) were preferentially expressed in hepatocytes in acinar zone 3 (the centrilobular region), whereas genes coding for CYP1A2, CYP2A, 2B and 2C were expressed uniformly throughout the liver acinus. In cirrhotic livers, CYP2A and 2B genes (and to a lesser extent, CYP3A genes) were highly expressed in isolated hepatocytes located at the junction of parenchyma with fibrous septa. The cause and significance of the position–dependent expression of specific cytochrome P–450 genes in normal and diseased human liver are discussed. (Hepatology 1992;16:682-687.)