Lymphocyte cytochrome P450 expression: inducibility studies in male Wistar rats.
The cytochrome P450 system plays a key role in the metabolism of endogenous and exogenous compounds. The system is distributed widely in body tissues, with the highest concentration of the enzymes found in liver hepatocytes. Extrahepatic expression of the P450 system has been documented in the lung, pancreas and kidney, and the enzymes are induced by many disease states, including diabetes mellitus and cancer. Little attention has been paid to the expression and inducibility of the system in peripheral blood lymphocytes. In this study, specific P450 inducers are administered in vivo to male Wistar rats. The expression and in vivo induction of the P450 isoforms CYP2B, CYP2E, CYP3A and CYP4A in liver and lymphocyte samples is determined using Western blot analysis. Following in vivo induction, the lymphocyte P450 proteins showed an average three-fold increase in expression (0.003-0.005 microg P450/microg microsomal protein), compared to the control lymphocyte samples. Expression in the induced lymphocyte samples was up to 11-fold lower than that in the induced liver samples, as expected. These results indicate that lymphocytes may provide a relatively simple method by which to monitor the P450 profile in human subjects.
Hannon-Fletcher
M P
MP
Northern Ireland Centre for Diet and Health, University of Ulster, Cromore Road, Coleraine, County Londonderry BT52 1SA, Northern Ireland, UK. mp.hannon@ulster.ac.uk
Barnett
Y A
YA
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D022781:Hepatocytes / Q000201:enzymology*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008861:Microsomes; D051381:Rats; D017208:Rats, Wistar
D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D042926:Cytochrome P-450 CYP4A