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Differential induction of cytochrome P-450 catalyzed activities by polychlorinated biphenyls and benzo [a]pyrene in B6C3F1 mouse liver and lung
Authors:C E Mitchell  J P Fischer  A R Dahl
Abstract:The properties of some constitutive and inducible enzyme activities of liver and lung microsomes were determined in B6C3F1 mice pretreated by either intratracheal (i.t.) administration of benzoa]pyrene (BaP) or polychlorinated biphenyl (PCBs) mixture (Aroclor 1254), or intraperitoneal (i.p.) administration with Aroclor 1254. After i.p. administration of Aroclor 1254, liver cytochrome P-450 content, aryl hydrocarbon hydroxylase (AHH), benzphetamine N-demethylase and nitroreductase activities were increased 2.8-, 2.0-, 2.2-, and 2.0-fold, respectively. Lung cytochrome P-450 content was also increased (1.9-fold) after i.p. administration of Aroclor 1254; AHH and nitroreductase activities, however, were not affected and benzphetamine N-demethylase activity was decreased. Aroclor 1254 administered i.t. did not affect liver cytochrome P-450 content. However, AHH and benzphetamine N-demethylase activities were decreased 1.4- and 1.2-fold, respectively, and nitroreductase activity was increased 1.6-fold. After i.t. administration of Aroclor 1254, lung cytochrome P-450 content and AHH activity were increased 1.4- and 2.2-fold, respectively. Benzphetamine N-demethylase activity was decreased 2.1-fold and nitroreductase activity was not affected. After i.t. administration of BaP, liver 7-ethoxyresorufin O-deethylase and nitroreductase activities were increased 2.2- and 1.5-fold, respectively, and benzphetamine N-demethylase activity was decreased 1.3-fold. Lung AHH and 7-ethoxyresorufin O-deethylase activities were increased 4.3- and 3.1-fold, respectively, and cytochrome P-450 content, benzphetamine N-demethylase and nitroreductase activities were decreased 1.4-, 1.2- and 1.3-fold, respectively, after BaP administration. These data indicate that different cytochrome P-450 isozymes induced in B6C3F1 mice are responsible for monooxygenase and nitroreductase activities, and that the route of administration of chemicals is important in the expression of cytochrome P-450 catalyzed activities.
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