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Fukuoka Igaku Zasshi ; 94(5): 174-82, 2003 May.
Article in Japanese | MEDLINE | ID: mdl-12872719

ABSTRACT

The in vivo metabolism of 2,3,3',4,4'-pentachlorobiphenyl (CB105) was studied in hamsters and the effect of cytochrome P450 inducers, phenobarbital (PB) and 3-methylcholanthrene (MC) on its metabolism was compared to rats. After administration of CB105 intraperitoneally at a dose of 3 mg/body, four metabolites, named M-1, M-2, M-3 and M-4, were detected in 5 days-feces of all groups and the formation ratio of the metabolites M-1-M-4 was 1:39:84:0.2 in untreated hamsters and 1:19:6.7:0.7 in untreated rats. On the basis of the mass spectra of four synthetic authentic compounds and the retention times on DB-1 and MPS50 columns, M-1, M-2, M-3 and M-4 were identified as 4'-hydroxy-2,3,3',4,5'-PenCB, 5'-hydroxy-CB105, 5-hydroxy-CB105 and 4-hydroxy-2,3,3',4',5-PenCB, respectively. The pretreatment of PB and MC resulted in about 2-fold fecal excretion of four metabolites in hamsters and in about 3-fold in rats. Of four metabolites, only M-4 were detected in the serum at 5 days after CB105 administration and the concentration was 0.39 microgram/ml of hamster serum and 0.28 microgram/ml of rat serum. In hamsters, the concentration of M-4 was increased to 1.8-fold of untreated animals by PB treatment and 2.6-fold by MC treatment. On the other hand, the treatment of rats with PB and MC did not show such an increase of serum M-4. These results suggested that the hamster oxidized 2,3,4-trichloro-substituted benzene ring predominantly rather than 3',4'-dichloro-substituted benzene ring differently from the rat and that M-4 formed in hamster liver distributed to the blood and retained there to a considerable extent in comparison with that formed in rat liver.


Subject(s)
Polychlorinated Biphenyls/metabolism , Animals , Cricetinae , Cytochrome P-450 Enzyme System/biosynthesis , Enzyme Induction/drug effects , Male , Mesocricetus , Methylcholanthrene/pharmacology , Microsomes, Liver/metabolism , Phenobarbital/pharmacology , Rats , Rats, Wistar , Species Specificity , Structure-Activity Relationship
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