INDUCTION AND REPRESSION OF CYTOCHROMES P 450 - IN-VIVO AND IN-VITRO METHODS

Induction of drug metabolism enzymes is defined as a de novo synthesis of an enzyme protein. Not all, but a certain number of sub-families o f cytochromes P450 are inducible among 27 families. Each group of indu cers is relatively specific of one corresponding P450 subfamily; Polic yclic hydrocarbons and P4501A; Phenobarbital and P4502B; glucocorticoi ds and P4503A; Ethanol and P4502E; Peroxisome proliferations and P4504 A. P450 induction has pharmacological implications specially concernin g drug interactions and inducers are themselves drugs of environmental compounds. Last 10 years have offered progresses in the knowledge of molecular mechanisms of induction such as mediation by receptors (Ah o r PPAR), transcriptional regulation ; Stabilisation of RNAm or of enzy me proteins. Repression of P450s synthesis is for less understood, as an example cytokines repress more than one P450-subfamily. At least tr anscriptional and post-translational mechanisms are involved.