Altered expression of cytochrome P450 and possible correlation with preneoplastic changes in early stage of rat hepatocarcinogenesis.
Acta Pharmacol Sin
; 26(6): 737-44, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15916741
ABSTRACT
AIM:
Correlation of cytochrome P450 (CYPs) with preneoplastic changes in the early stage of hepatocarcinogenesis is still unclear. To detect the expression of carcinogen-metabolizing related microsomal P450 enzymes, namely the CYP1A1, CYP1A2, CYP2B1/2, CYP2E1, and CYP3A, we performed the medium-term bioassay of Ito's model in Sprague-Dawley rats.METHODS:
The amount and activity of CYP were assessed by biochemical and immunohistochemical methods in week 8. The correlation between CYP expression and microsomal oxidative stress was investigated by comparing the generation of microsomal lipid peroxidation in the presence or absence of specific CYP inhibitor.RESULTS:
In the DEN-2-AAF and 2-AAF alone groups, the expression of CYP1A1 and CYP2E1 were up-regulated and the expression of CYP2B1/2 and CYP1A2 were quite the contrary. Strong staining of CYP2E1 and CYP2B1/2 was found around the centrolobular vein and weak staining in the altered hepatic foci revealed by immunohistochemical procedure. There was no significant change in the activity of CYP3A among the 4 groups. Altered hepatic tissue bore more microsomal NADPH (nicotinamide adenine dinucleotide phosphate,reduced form)-dependent lipid peroxidation than normal tissue. And the difference among the 4 groups disappeared when CYP2E1 was inhibited. More microsomal lipid peroxidation was generated when incubated with CYP1A inhibitor a-naphthoflavone.CONCLUSION:
CYP altered their expression levels and these alterations can play important roles in the alteration of cell redox status of preneoplastic tissue in the early stage of hepatocarcinogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Microssomos Hepáticos
/
Cocarcinogênese
/
Citocromo P-450 CYP2E1
/
Neoplasias Hepáticas Experimentais
Limite:
Animals
Idioma:
En
Revista:
Acta Pharmacol Sin
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
China