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 insights into the substrate specificity of induced CYPs. Marked species- and sex-related differences in the inducibility of PROD activity by tested chemicals were observed, the mouse being always more responsive when compared to hamster or rat. Induction by sodium phenobarbital (NaPB) led to a conspicuous increase in all situations, up to approximately 38-fold in female rat and mouse liver, with the exception of hamster kidney where PROD activity was only slightly affected. Unexpectedly, both sodium barbital (NaB) and phorone (PHR) moderately induce CYP2B1 isoforms in rat, the extent being highest in female kidney (PHR, 14-fold increase) and male lung (NaB, 4.5-fold). The degree of induction was maximal in the liver with some exceptions occurring in male mice where NaB 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 activity as specific enzymatic assay to probe CYP2B1-like induction.
Paolini
M
M
Department of Pharmacology, University of Bologna, Italy.
Mesirca
R
R
Pozzetti
L
L
Sapone
A
A
Cantelli-Forti
G
G
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001462:Barbital / Q000494:pharmacology / Q000633:toxicity; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity; D006224:Cricetinae; D003520:Cyclophosphamide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D004000:Dichloroethylenes / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007659:Ketones / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013045:Species Specificity; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D013379:Substrate Specificity
D002273:Carcinogens; D004000:Dichloroethylenes; D007659:Ketones; D008748:Methylcholanthrene; D001462:Barbital; C018637:phorone; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase; D004128:Dimethylnitrosamine; C035384:1,2-dichloroethylene; D010634:Phenobarbital