Time course of oxidative benz[a]anthracene metabolism by liver microsomes of normal and PCB-treated rats. 1981

J Jacob, and A Schmoldt, and G Grimmer

The time course for the oxidative metabolism of benz[a]anthracene by liver microsomes of normal, 3,3',4,4'-tetrachlorobiphenyl-(TCBP) and polychlorinated biphenyl-(PCB) treated rats has been investigated. These are shown not to be linear in all cases. In normal microsomes the 10,11-dihydrodiol is the main metabolite, followed by the 5,6- and 8,9-dihydrodiols. Secondary metabolism, i.e. formation of dihydrodiol epoxides, is observed only after 5 min. In contrast, TCBP microsomes produced predominantly the 5,6-dihydrodiol followed by the 8,9-dihydrodiol, whereas the formation of the 10,11-dihydrodiol is suppressed. Metabolism deriving from oxidation of the 5,6-position is increased 15-20 fold; again secondary metabolites occur between the 5th and 10th min of incubation. Gas chromatography and mass spectra data suggests the formation of the ultimate carcinogen, 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracene, as concluded from detection of its rearrangement product, the 2,3,4-triol. In PCB-treated rats secondary metabolism is observed within 2.5 min. 5,6-Oxidation is increased 27 fold, 8,9-oxidation 10 fold, but 10,11-oxidation is completely suppressed. The above-mentioned ultimate carcinogen is also formed. Moreover, a series of tetrols is detected. Optimum incubation times dependent on the problem under study are discussed.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D011078 Polychlorinated Biphenyls Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001551 Benz(a)Anthracenes Four fused benzyl rings with three linear and one angular, that can be viewed as a benzyl-phenanthrenes. Compare with NAPHTHACENES which are four linear rings. Benz(b)Phenanthrenes,Naphthanthracenes
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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