Metabolism of benzo(a)pyrene by variant mouse hepatoma cells. 1985

E L Schaefer, and J K Selkirk

Four mouse hepatoma cell lines, a parent (Hepa-1c1c7) and three variants (MUL12, BPrc1, and TAOc1BPrc1) which had been derived from Hepa-1c1c7 by the fluorescence-activated cell sorter, were incubated with benzo(a)pyrene, and the metabolites were analyzed by high-pressure liquid chromatography. Among these four cell lines, Hepa-1c1c7 and MUL12 metabolized benzo(a)pyrene the most quickly and to the greatest extent, and BPrc1 had the weakest metabolic activity for this substrate. TAOc1BPrc1 had intermediate benzo(a)pyrene-metabolizing activity, depending on cell density and incubation time. At low cell density, the active variant TAOc1Bprc1 resembled the weakly active Bprc1 in accumulating a low amount of ethyl acetate-soluble metabolites in the medium while, at high cell density, TAOc1Bprc1 resembled the parent clone Hepa-1c1c7 and the highly active variant MUL12. At short incubation times, TAOc1Bprc1 also had low conjugating activity while, at longer incubation times, the conjugating activity approached that of Hepa-1c1c7 and MUL12. At low cell density, Bprc1 was able to produce phenols, but this variant did not seem to have this ability at high cell density. When the substrate concentration was 4 microM and the incubation time was 24 h, beta-glucuronidase treatment of water-soluble metabolites released about 5.3 times more pmol of quinones compared with phenols. But when the substrate concentration was 25 nM, beta-glucuronidase released about 2.0 times as many phenols compared with quinones. The parent and the two more actively metabolizing variants showed differences in the peak times of accumulation of 9,10-diol and 7,8-diol of benzo(a)pyrene, which may have implications for binding to DNA and nuclear proteins. It was concluded that BPrc1 has basal but not easily inducible aryl hydrocarbon hydroxylase activity, whereas Hepa-1c1c7, MUL12, and TAOc1Bprc1 have basal and inducible aryl hydrocarbon hydroxylase activity. These results show that variants of a single parent cell line can exhibit significant differences in the rate and extent of metabolism of benzo(a)pyrene.

UI MeSH Term Description Entries
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D005966 Glucuronidase Endo-beta-D-Glucuronidase,Endoglucuronidase,Exo-beta-D-Glucuronidase,beta-Glucuronidase,Endo beta D Glucuronidase,Exo beta D Glucuronidase,beta Glucuronidase
D000085 Acetates Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure. Acetate,Acetic Acid Esters,Acetic Acids,Acids, Acetic,Esters, Acetic Acid
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
D001189 Aryl Hydrocarbon Hydroxylases A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides. Microsomal Monooxygenases,Xenobiotic Monooxygenases,Hydroxylases, Aryl Hydrocarbon,Monooxygenases, Microsomal,Monooxygenases, Xenobiotic
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D014316 Tritium The radioactive isotope of hydrogen also known as hydrogen-3. It contains two NEUTRONS and one PROTON in its nucleus and decays to produce low energy BETA PARTICLES. Hydrogen-3,Hydrogen 3
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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