{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:37:24Z","timestamp":1777894644855,"version":"3.51.4"},"reference-count":22,"publisher":"SAGE Publications","issue":"1_suppl","license":[{"start":{"date-parts":[[2001,1,1]],"date-time":"2001-01-01T00:00:00Z","timestamp":978307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1080\/019262301753178573","type":"journal-article","created":{"date-parts":[[2003,1,29]],"date-time":"2003-01-29T23:23:13Z","timestamp":1043882593000},"page":"161-172","source":"Crossref","is-referenced-by-count":12,"title":["Comparison of the Levels of Enzymes Involved in Drug Metabolism between Transgenic or Gene-knockout and the Parental Mice"],"prefix":"10.1177","volume":"29","author":[{"given":"Noritaka","family":"Ariyoshi","sequence":"first","affiliation":[{"name":"Laboratory of Drug Metabolism, Graduate School of Pharmaceutical\rSciences, Hokkaido University, Sapporo 060-0812, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susumu","family":"Imaoka","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology, Osaka City University\rMedical School, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Metabolism, Graduate School of Pharmaceutical\rSciences, Hokkaido University, Sapporo 060-0812, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Metabolism, Graduate School of Pharmaceutical\rSciences, Hokkaido University, Sapporo 060-0812, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken-Ichi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Metabolism, Graduate School of Pharmaceutical\rSciences, Hokkaido University, Sapporo 060-0812, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiko","family":"Funae","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology, Osaka City University\rMedical School, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Kamataki","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Metabolism, Graduate School of Pharmaceutical\rSciences, Hokkaido University, Sapporo 060-0812, Japan, kamataki@pharm.hokudai.ac.jp"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2001,1,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2744(199606)16:2<63::AID-MC1>3.0.CO;2-O"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(99)00125-1"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1177\/019262330002800613"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(89)90395-X"},{"key":"atypb5","first-page":"265","volume":"193","year":"1951","journal-title":"Anal Biochem"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)82245-5"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)82244-3"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)73803-4"},{"key":"atypb9","doi-asserted-by":"crossref","unstructured":"Burchell B., Weatherill P. 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