Differential induction of mRNA expression of cytochromes P450 (CYP2B1 and CYP1A1/2) by metyrapone in primary rat hepatocyte cultures.
Res Commun Mol Pathol Pharmacol
; 94(1): 47-61, 1996 Oct.
Article
em En
| MEDLINE
| ID: mdl-8948014
ABSTRACT
The mRNA expression of members of two cytochrome P450 (CYP) gene subfamilies involved in carcinogen activation, the CYP1A1/2 and CYP2B1 forms, was determined in primary rat hepatocyte cultures in response to metyrapone and to the inducer phenobarbital or 5,6-benzoflavone (BNF), respectively. Incubation of cells with 0.5 mM metyrapone resulted in accumulation of CYP1A1 and CYP1A2 mRNA and in a marked increase in CYP1A-associated enzymatic activity as determined by deethylation of ethoxyresorufin. Metyrapone and phenobarbital in combination acted synergistically in elevation of ethoxyresorufin O-deethylase activity. In hepatocytes treated with metyrapone or with phenobarbital, accumulation of CYP2B1 mRNA levels preceded an increase in CYP2B-associated, pentoxyresorufin O-depentylase activity. However, CYP2B1 mRNA levels were first detectable after 24 hours of treatment with phenobarbital, whereas metyrapone elicited a substantial increase in mRNA levels within 14 hours, suggesting differing mechanisms leading to accumulation of CYP2B1 mRNA under the two inducers.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Citocromo P-450 CYP1A1
/
Citocromo P-450 CYP1A2
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Citocromo P-450 CYP2B1
/
Fígado
/
Metirapona
Limite:
Animals
Idioma:
En
Revista:
Res Commun Mol Pathol Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article