Comparative study of CYP2B induction in the liver of rats and mice by different compounds.
Male Wistar rats and C57BL mice were treated by phenobarbital (PB), 2,4,6-triphenyldioxane-1,3 (TPD) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). The CYP2B specific activities (PROD and BROD) were determined in the animal livers. PB administration significantly increased levels of PROD- and BROD-activity in the rat and mouse livers, whereas TPD induced CYP2B activities only in rat liver and TCPOBOP--only in mouse liver. The result of Western-blot analysis showed that PB and TPD increased CYP2B protein content in rat liver, PB and TCPOBOP--in mouse liver. Results of multiplex RT-PCR showed that the increase in CYP2B enzymatic activities reflected at least in part an increased mRNA levels. Thus, our results provide evidence to support the conclusion that the species-dependent differences of CYP2B induction occur because of differences of transcriptional activation of CYP2B genes.
Pustylnyak
Vladimir O
VO
Institute of Molecular Biology and Biophysics, Timakova str., 2, Novosibirsk 630117, Russia. pustylnyak@ngs.ru
Lebedev
Anton N
AN
Gulyaeva
Lyudmila F
LF
Lyakhovich
Vyacheslav V
VV
Slynko
Nikolaj M
NM
D000818:Animals; D015153:Blotting, Western; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis* / Q000235:genetics; D004146:Dioxanes / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010634:Phenobarbital / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D015533:Transcriptional Activation / Q000187:drug effects; D015262:Xenobiotics / Q000494:pharmacology*
D004146:Dioxanes; D011725:Pyridines; D012333:RNA, Messenger; D015262:Xenobiotics; C054589:2,4,6-triphenyl-1,3-dioxane; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene; D019362:Cytochrome P-450 CYP2B1; D010634:Phenobarbital