INDUCTION OF CYP2B1 MEDIATED PENTOXYRESORUFIN O-DEALKYLASE ACTIVITY IN DIFFERENT SPECIES, SEX AND TISSUE BY PROTOTYPE 2B1-INDUCERS

The induction of CYP2B1 mediated pentoxyresorufin O-dealkylase (PROD) activity by various xenobiotics was explored in liver, kidney and lung from a variety of animal species of both sexes, in order to gain insi ghts into the substrate specificity of induced CYPs. Marked species- a nd sex-related differences in the inducibility of PROD activity by tes ted chemicals were observed, the mouse being always more responsive wh en compared to hamster or rat. Induction by sodium phenobarbital (NaPB ) led to a conspicuous increase in-all situations, up to similar to 38 -fold in female rat and mouse liver, with the exception of hamster kid ney where PROD activity was only slightly affected. Unexpectedly, both sodium barbital (NaB) and phorone (PHR) moderately induce CYP2B1 isof orms in rat, the extent being highest in female kidney (PHR, 14-fold i ncrease) and male lung (NaB, 4.5-fold). The degree of induction was ma ximal in the liver with some exceptions occurring in male mice where N aB induced up to 46- and 115-fold increases in lung and kidney and PHR up to 115-fold in kidney. Minimal, although significant induction of PROD activity following treatment with trans-1,2-dichloroethylene (1,2 - DCE) occurred in all situations with the exception of hamster kidney and lung. Therefore, caution should be exercised when using PROD acti vity as specific enzymatic assay to probe CYP2B1-like induction.