Hepatic drug metabolizing enzymes induced by clofibrate in rasH2 mice.
Hepatic drug metabolizing enzyme activities were determined, after treatment with clofibrate, in transgenic mice carrying human c-Ha-ras (rasH2 mice). Changes in the drug metabolizing enzyme activities in these mice by gene integration were also evaluated. Male and female rasH2 mice (Tg) and the litter mates not carrying the gene (non-Tg) received orally 500 mg/kg of clofibrate or the vehicle for 12 consecutive days. Liver homogenate and microsomes were prepared and the contents and activities of cytochrome P450 (CYP), cytochrome b5 content and enzyme activities related to peroxisome proliferation were determined. Relative liver weights, CYP4A and activities of catalase and carnitine palmitoyl transferase increased to the same extent in Tg and non-Tg mice treated with clofibrate. In Tg and non-Tg groups that received vehicle, contents and activities of CYP and cytchrome b5 contents were comparable. It was concluded that gene integration did not alter drug metabolizing enzymes and responses to clofibrate.
Katsutani
N
N
Department of Developmental Safety Assessment Research, Eisai Company, Gifu, Japan. n-katsutani@hhc.eisai.co.jp
Sekido
T
T
Aoki
T
T
Sagami
F
F
D000818:Animals; D000924:Anticholesteremic Agents / Q000633:toxicity; D015197:Carcinogenicity Tests; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis; D002374:Catalase / Q000096:biosynthesis; D002994:Clofibrate / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D015786:Cytochromes b5 / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D020025:Peroxisome Proliferators / Q000633:toxicity
D000924:Anticholesteremic Agents; D020025:Peroxisome Proliferators; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D002334:Carnitine O-Palmitoyltransferase; D002994:Clofibrate