Mouse hepatic cytochrome P-450 isozyme induction by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, pyrazole, and phenobarbital

Raunio, H., Kojo, A., Juvonen, R., Honkakoski, P., Jarvinen, P., Lang, M. A., Vahakangas, K., Gelboin, H. V., Park, S. S. and Pelkonen, O. (1988) Mouse hepatic cytochrome P-450 isozyme induction by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, pyrazole, and phenobarbital. Biochemical Pharmacology, 37 21: 4141-4147. doi:10.1016/0006-2952(88)90108-6


Author Raunio, H.
Kojo, A.
Juvonen, R.
Honkakoski, P.
Jarvinen, P.
Lang, M. A.
Vahakangas, K.
Gelboin, H. V.
Park, S. S.
Pelkonen, O.
Title Mouse hepatic cytochrome P-450 isozyme induction by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, pyrazole, and phenobarbital
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
1873-2968
Publication date 1988-11
Sub-type Article (original research)
DOI 10.1016/0006-2952(88)90108-6
Volume 37
Issue 21
Start page 4141
End page 4147
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract The effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and pyrazole on mouse hepatic cytochrome P-450 isozyme expression were compared to the P-450 induction pattern elicited by phenobarbital. TCPOBOP and PB administration caused a similar induction profile by increasing microsomal protein and cytochrome P-450 content and the catalytic activities of several monooxygenases in DBA/2N and AKR/J mice. There were, however, several quantitative and some qualitative differences in the induction profile caused by phenobarbital and TCPOBOP. A few strain-related differences were also observed. Immunoblot analysis with polyclonal anti-coumarin hydroxylase (P-450Coh) antibody and epitope-specific monoclonal antibodies 1-7-1 and 2-66-3 showed that both phenobarbital and TCPOBOP increase the amount of P450IIB and P-450Coh. TCPOBOP caused a more pronounced increase in the amount of P-450IIB than phenobarbital, and TCPOBOP also caused an increase in the amount of P-450IA2. These data suggest that in the mouse, TCPOBOP increases mainly the expression of P-450 isozymes responsive to phenobarbital. The effects of pyrazole differed greatly from those caused by TCPOBOP and phenobarbital. In the DBA/2N mice, pyrazole increased coumarin 7-hydroxylation 9.4-fold, whereas in the AKR/J mice the activity was induced only to a level equivalent to the DBA/2N basal level. In immunoblot experiments with anti-P-450Coh antibody, the amount of P-450Coh was considerably higher in DBA/2N mice treated with phenobarbital, TCPOBOP, or pyrazole in comparison with the AKR/J mice, indicating a strain specificity in the inducibility of coumarin 7-hydroxylase by pyrazole.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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