Biochemical characterization of the hepatic effects in mice and rats of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a hepatic neoplasm promoter.
The biochemical effects on the liver of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), a phenobarbital-like enzyme inducer, were studied in the mouse and rat. In mice a single dose of TCPOBOP (3 mg/kg, ip) caused marked and long-lasting (at least 7 days) induction of liver cytochrome P-450, 7-ethoxycoumarin-O-deethylase, and epoxide hydrolase. TCPOBOP had much less effect in rats than in mice, even at a higher dose (30 mg/kg) TCPOBOP also induced DNA synthesis in mice and rats but ornithine decarboxylase activity only in mice. In addition, in mice but not in rats, TCPOBOP increased microsomal membrane fluidity, as detected by fluorescence polarization measurements.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D004851:Epoxide Hydrolases / Q000096:biosynthesis*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010105:Oxygenases / Q000096:biosynthesis*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D013045:Species Specificity
D002273:Carcinogens; D011725:Pyridines; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D004851:Epoxide Hydrolases; D009955:Ornithine Decarboxylase