2-4-6-triphenyl-1-3-dioxane and 1-4-bis(2-(3-5-dichloropyridyloxy))benzene

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.

Topics: Animals; Blotting, Western; Cytochrome P-450 CYP2B1; Dioxanes; Enzyme Induction; Liver; Male; Mice; Mice, Inbred C57BL; Models, Animal; Phenobarbital; Pyridines; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Species Specificity; Transcriptional Activation; Xenobiotics

The induction by triphenyldioxane (TPD) of cytochrome P-450 in rat liver microsomes was studied. It was demonstrated that TPD injection in a single dose (10 mg/kg of body mass) is associated with a marked induction of cytochromes P-450 b/e (cytochrome PB-forms) in rat liver microsomes and a significant increase in the benzphetamine-N-demethylase activity typical of cytochrome P-450b. In other words, TPD is a potent inducer of PB-type, the inducing effect being attained by an injection of a single dose of TPD which is by one order of magnitude less than that of phenobarbital. It can be assumed that this compound shows a high affinity for the hypothetical receptor responsible for cytochrome P-450b synthesis. It was shown also that TPD does not induce the monooxygenase system of mouse liver, whereas 1,4-bis[2-(dichloropyridyloxy)]benzene (DPB) is a potent inducer of PB-type in mice, being fairly ineffective in rats. Hence, the species-specific effect of TPD and DPB appears to be opposite.

Topics: Animals; Cytochrome P-450 Enzyme System; Dioxanes; Dioxins; Enzyme Induction; Isoenzymes; Male; Microsomes, Liver; Phenobarbital; Pyridines; Rats; Rats, Inbred Strains