2000 年 15 巻 1 号 p. 46-51
Cytochrome P450s (P450s) are induced by drugs, environmental chemicals, diseases, and genetic factors. Changes in the levels of P450 have a significant effect on the pharmacokinetics or pharmacodynamics of drugs and endogenous substrates. In experimental animals such as a rat, induction of P450 is detected in hepatic microsomes by drug metabolism assay and Western blotting with antibodies. Assay system of multiple P450 isoforms with Western blotting has been established but it is difficult to apply this method to human subjects because human hepatic tissue must be isolated to assay P450 induction. We tried to develop a less-invasive assay for detection of P450 induction. Detection system of P450 mRNA induction in human lymphocytes in peripheral blood was established using by a competitive PCR or a real-time PCR. Induction of CYP2E1 and CYP3A4 by diabetes and rifampicin, respectively, was detected by this method.