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Induction of cytophromes P450 1A, P450 2B, and P450 3A in long-evans rats by low-level exposure to aroclor 1260

University of British Columbia

Poly chlorinated biphenyls (PCBs) are highly persistent environmental contaminants that are capable of inducing cytochrome P450 enzymes in exposed animals. In the present study, one set of male Long-Evans rats was treated with various doses of Aroclor 1260 ranging from 0.5 to 50 mg/kg in an attempt to achieve a level of exposure similar to that observed in the environment. Treatment was via oral gavage for seven days followed by sacrifice three days later. A second set of rats was treated at a dose of 10 mg/kg using the same protocol, but were killed from one to 48 days after the last treatment. Total cytochrome P450 content and several cytochrome P450 mediated enzyme activities were measured. Significant increases in enzyme activities indicative of cytochrome P450 2B were found at doses of 5.0 mg/kg and greater. Immunoquantitation of blots probed with antibody to P450 2B1 confirmed a marked induction of cytochrome P450 2B isozymes at doses of 5 mg/kg and greater. Dose-dependent increases in cytochrome P450 1A1 protein levels and cytochrome P450 lA-mediated enzyme activities were observed. Enzyme activities catalyzed by cytochrome P450 3A and immunoreactive cytochrome P450 3A protein were increased significantly by Aroclor 1260 treatment at doses of 5.0 mg/kg and greater. Cytochrome P450 1A1 and P450 3A levels correlated with hepatic PCB levels, while there was no more than a weak correlation between hepatic PCB levels and cytochrome P450 2B levels. Significant increases in cytochrome P450 2B-mediated activities and protein levels persisted for at least 48 days post-treatment. Induction of cytochrome P450 1 A l protein levels and enzyme activities was relatively short-lived, while cytochrome P450 3A protein levels and enzyme activities were increased significantly for up to 24 days post-treatment. In summary, the study indicates that subchronic low-level exposure to Aroclor 1260 induces cytochromes P450 1A, P450 2B, and P450 3A enzymes, but that cytochrome P450 2B1 is induced to the greatest extent and the induction is more persistent.

Thesis/Dissertation

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2009-04-28

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http://hdl.handle.net/2429/7637

Pharmaceutical Sciences

University of British Columbia

UBCV

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