Studies of the Expression of the Cytochrome P450IA, P450IIB, and P450IIC Gene Family in Extrahepatic and Hepatic Tissues

Abstract

We have studied the expression of three P-450 gene subfamilies in hepatic and extrahepatic tissues using the sensitive RNAse A protection assay. Members of the P4501A subfamily, which encodes the major methylcholanthrene-inducible cytochromes P-450, were found to be not expressed in extrahepatic tissues of untreated animals, raising the question whether these P-450 play a role in the metabolism of carcinogens in unexposed individuals. In contrast, members of the P45011B family, some of which encode the major phenobarbital-inducible cytochromes P-450, were found to be expressed in some extrahepatic tissues of untreated rats and here most notably in the lung and in sebaceous glands. Members of the P450IIC family, which encode some constitutively expressed cytochromes P-450, were found to be expressed exclusively in the liver.

Multi-parametric analysis of cytochrome P450 expression in rat liver microsomes by LA-ICP-MS

“…1 The profiles of CYP enzymes are variable and show clear organ specificities with respect to composition and enzyme levels. 2,3 Furthermore, the adaptive responsivity of the system on exposure to xenobiotics is an important feature meaning that compounds may initiate their own metabolism by induction of a respective CYP enzyme. Shortly after the discovery of the cytochrome P450 in 1958 by Klingenberg 4 and colleagues it became obvious that it is not a single protein but a family of proteins, an aspect nicely summarised in a historical review by Estabrook.…”