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Research article

Genetic analysis of the phenobarbital regulation of the cytochrome P-450 2b-9 and aldehyde dehydrogenase type 2 mRNAs in mouse liver

Marie DAMON, Alain FAUTREL, André GUILLOUZO, Laurent CORCOS
Biochemical Journal Jul 15, 1996, 317 (2) 481-486; DOI: 10.1042/bj3170481
Marie DAMON
Equipe Détoxication et Réparation Tissulaire, Faculté de Pharmacie, Université de Rennes I and INSERM U49, CHRU Pontchaillou, 35033 Rennes Cedex, FranceINRA, Station de Recherche Porcine, 35590 St. Gilles, France
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Alain FAUTREL
Equipe Détoxication et Réparation Tissulaire, Faculté de Pharmacie, Université de Rennes I and INSERM U49, CHRU Pontchaillou, 35033 Rennes Cedex, France
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André GUILLOUZO
Equipe Détoxication et Réparation Tissulaire, Faculté de Pharmacie, Université de Rennes I and INSERM U49, CHRU Pontchaillou, 35033 Rennes Cedex, France
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Laurent CORCOS
Equipe Détoxication et Réparation Tissulaire, Faculté de Pharmacie, Université de Rennes I and INSERM U49, CHRU Pontchaillou, 35033 Rennes Cedex, France
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Abstract

The aim of this study was to investigate the effect of the genetic background on the phenobarbital inducibility of cytochrome P-450 2b-9, cytochrome P-450 2b-10 and aldehyde dehydrogenase type 2 mRNAs in mice. We analysed the basal expression and the phenobarbital inducibility of both cytochrome P-450 mRNAs by semi-quantitative specific reverse transcription-PCR analyses in five inbred mouse strains (A/J, BALB/cByJ, C57BL/6J, DBA/2J and SWR/J). Male mice constitutively expressed cytochrome P-450 2b-9 and cytochrome P-450 2b-10 mRNAs, but a number of differences in their response to phenobarbital were observed. In all these mouse strains, phenobarbital induced cytochrome P-450 2b-10 mRNA whereas it could have either a positive or a negative effect on cytochrome P-450 2b-9 expression, depending on the strain and the sex of the mice. Specifically, phenobarbital increased cytochrome P-450 2b-9 expression in C57BL/6J males while it decreased it in DBA/2J mice. Interestingly, dexamethasone was able to mimic the phenobarbital effect on both cytochromes P-450 in these two strains. Aldehyde dehydrogenase type 2 mRNA was always induced by phenobarbital, except in the C57BL/6J strain. Genetic analysis revealed that the phenobarbital-inducible phenotype was either a semi-dominant or a recessive trait in F1 animals from a C57BL/6J×DBA/2J cross for the cytochrome P-450 2b-9 and the aldehyde dehydrogenase type 2 genes, respectively. This study suggests that the genetic basis for phenobarbital induction in mice depends on the target gene, and that more than one regulatory step would be involved in this response pathway.

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July 1996

Volume: 317 Issue: 2

Biochemical Journal: 317 (2)
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Genetic analysis of the phenobarbital regulation of the cytochrome P-450 2b-9 and aldehyde dehydrogenase type 2 mRNAs in mouse liver
Marie DAMON, Alain FAUTREL, André GUILLOUZO, Laurent CORCOS
Biochemical Journal Jul 1996, 317 (2) 481-486; DOI: 10.1042/bj3170481
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Genetic analysis of the phenobarbital regulation of the cytochrome P-450 2b-9 and aldehyde dehydrogenase type 2 mRNAs in mouse liver
Marie DAMON, Alain FAUTREL, André GUILLOUZO, Laurent CORCOS
Biochemical Journal Jul 1996, 317 (2) 481-486; DOI: 10.1042/bj3170481

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