Details

Autor(en) / Beteiligte

• Ariyoshi, Noritaka
• Imaoka, Susumu
• Nakayama, Kazuo
• Takahashi, Yoshiki
• Fujita, Ken-Ichi
• Funae, Yoshihiko
• Kamataki, Tetsuya

Titel

Comparison of the Levels of Enzymes Involved in Drug Metabolism between Transgenic or Gene-knockout and the Parental Mice

Ist Teil von

• Toxicologic pathology, 2001, Vol.29 (1_suppl), p.161-172

Ort / Verlag

Los Angeles, CA: SAGE Publications

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 orXPA 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.