Comparison of the levels of enzymes involved in drug metabolism between transgenic or gene-knockout and the parental mice.
Toxicol Pathol
; 29 Suppl: 161-72, 2001.
Article
em En
| MEDLINE
| ID: mdl-11695553
ABSTRACT
Drug-metabolizing enzymes are involved in the metabolic activation or detoxification of carcinogens. To evaluate animals developed as models for alternative carcinogenicity testing, we investigated whether or not a gene manipulation including the transgene of ras and the knocking out of a tumor suppressor gene such as p53 or XPA could alter the expression of representative drug-metabolizing enzymes directly or indirectly. Expression of several isoforms of cytochrome P450 (CYP) in the liver of rasH2, p53 (+/-), Tg.AC, and XPA (-/-) mice with or without treatment of prototype inducer. phenobarbital or 3-methylcholanthrene, was analyzed by Western immunoblotting in comparison with their parental strains of mice. In addition, the activities of 3 major phase II enzymes, UDP-glucronosyltransferase, sulfotransferase, and glutathione S-transferase, were compared between the gene-manipulated and the corresponding parental strains of mice. Results demonstrate that XPA gene knockout appeared to increase constitutive expression of CYP2B and CYP3A isoforms. Overexpression of human c-Ha-ras gene or p53 gene knockout appeared to increase constitutive UGT activity toward 4-nitrophenol. The content or activities of almost all other enzymes examined in the present study do not appear to be affected by the gene manipulation.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Testes de Carcinogenicidade
/
Sistema Enzimático do Citocromo P-450
/
Modelos Animais de Doenças
/
Fígado
Tipo de estudo:
Evaluation_studies
Limite:
Animals
Idioma:
En
Revista:
Toxicol Pathol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Japão