Differential enzyme induction of mouse liver and lung following a single low or high dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Journal of Biochemical Toxicology
L E BeebeL M Anderson

Abstract

The induction response of cytochrome P-450-dependent enzyme activities to a single low (5 nmol/kg) or high (50 nmol/kg, intraperitoneal [ip] dose of TCDD was examined in liver and lung homogenates over a 12-week time course in an outbred, Ah-responsive strain of mice (National Institutes of Health [NIH] Swiss). Total hepatic cytochrome P-450 was quantified, and the dealkylation of ethoxy- and benzyloxyresorufin (activities of P-450 IA1 and IIB1, respectively) were measured in both tissues at 48 and 96 hr and at 1, 4, and 12 weeks post-TCDD administration. Western immunoblotting with monoclonal antibody 1-7-1 was conducted to confirm the specific IA1-inductive effects of each dose of TCDD over the same time course. Following the low dose, specific IA1 induction was apparent in liver at the earliest time point, was maximal at 1 week, and declined to control values at 12 weeks. Pulmonary IA1 was near-maximally induced at 48 hr, and remained at that level for 4 weeks. In contrast, a tenfold higher dose of TCDD elicited similar IA1 induction profiles for both tissues, with a maximum at 1 week and a progressive loss at 4 and 12 weeks postexposure. P-450 IIB1 activity was elevated in TCDD-treated animals by enzymatic assay; however, W...Continue Reading

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Citations

May 1, 1992·Toxicology and Applied Pharmacology·L BeebeL M Anderson
Jun 23, 1993·Annals of the New York Academy of Sciences·D W NebertV Vasiliou
Mar 29, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sabine TeskeB Paige Lawrence
Jul 14, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jay S Petrick, Curtis D Klaassen

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