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)pyrene and Phenobarbital Pretreatment on the Biliary Excretion of Benzo(
)pyrene Metabolites in the Rat1
The Wellcome Research Laboratories, Burroughs Wellcome & Co. (U. S. A.) Inc., Tuckahoe, New York 10707
Benzo(
)pyrene (BP) metabolites are excreted into the bile at a slower rate after an i.v. injection of 14C-labeled BP than after an injection of 14C-labeled biliary metabolites of BP. Pretreatment of rats with BP or phenobarbital prior to the i.v. injection of 10 or 300 µg of BP-14C enhances the rate of excretion of metabolites of BP-14C into the bile. No effect of pretreatment was observed when 14C-labeled metabolites of BP, instead of BP-14C, were injected i.v., which indicates that pretreatment with BP or phenobarbital does not enhance the transport of BP metabolites into bile but enhances the formation of BP metabolites. The results described in this manuscript and elsewhere (14) indicate that pretreatment of rats with BP enhances the in vivo hydroxylation of BP-14C, whereas phenobarbital does not exert this effect. The data suggest that treatment of rats with phenobarbital prior to the administration of BP-14C may enhance the biliary excretion of BP-14C metabolites by enhancing the conjugation of hydroxylated BP metabolites.
1 Supported in part by Research Contract PH 43-65-1066 from the Pharmacology-Toxicology Programs, National Institute of General Medical Sciences, NIH.
2 Present address: Pharmakologisches Institut der Freien Universität, (Abt. Embryonal-Pharmakologie), 1 Berlin-Dahlem (33), Thielallee 69/73, West Germany.
3 Present address: Department of Biochemistry, Hoffmann-La Roche, Inc., Nutley, N. J. 07110.
Received 5/ 1/70. Accepted 8/19/70.
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