التفاصيل البيبلوغرافية
| العنوان: |
Comparison of the Levels of Enzymes Involved in Drug Metabolism between Transgenic or Gene-knockout and the Parental Mice. |
| المؤلفون: |
Ariyoshi, Noritaka, Imaoka, Susumu, Nakayama, Kazuo, Takahashi, Yoshiki, Fujita, Ken-Ichi, Funae, Yoshihiko, Kamataki, Tetsuya |
| المصدر: |
Toxicologic Pathology; Sep/Oct2001 Supplement, Vol. 29, p161-172, 12p, 4 Charts, 9 Graphs |
| مصطلحات موضوعية: |
CARCINOGENS, CARCINOGENICITY testing, TRANSGENES, RAS oncogenes, RATS, GENETICS, METABOLISM |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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