Characterization of a human teratocarcinoma cell assay for inhibitors of metabolic cooperation. 1986

T J Kavanagh, and C C Chang, and J E Trosko

Although a Chinese hamster V79 cell-based assay for inhibitors of metabolic cooperation is currently available, the development of a human cell-based assay is desirable in order to avoid inappropriate extrapolation from animal cells to human cells. Cells derived from a human teratocarcinoma cell line (designated PA-1), which has a stable pseudodiploid karyotype and excellent in vitro growth properties, were used in a metabolic cooperation assay. The assay was based on the metabolic isolation of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient variants in the presence of HGPRT-proficient cells and 6-thioguanine. Chemicals which inhibit the transfer of the lethal metabolite of 6-thioguanine from HGPRT-proficient to HGPRT-deficient cells will allow for recovery of the 6-thioguanine-resistant (HGPRT-deficient) cells. Chemicals tested included 12-O-tetradecanoylphorbol-13-acetate and related analogues phorbol-12,13-didecanoate, mezerein, and 4-phorbol-12,13-didecanoate. Concurring with results previously obtained in V79 cells, 12-O-tetradecanoylphorbol-13-acetate and phorbol-12,13-didecanoate strongly inhibited metabolic cooperation, whereas mezerein was moderately inhibitory and 4 alpha-phorbol-12,13-didecanoate was inactive. These cells thus hold promise as a human cell-based assay for inhibitors of metabolic cooperation.

UI MeSH Term Description Entries
D007041 Hypoxanthine Phosphoribosyltransferase An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or MERCAPTOPURINE to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8. Guanine Phosphoribosyltransferase,HPRT,Hypoxanthine-Guanine Phosphoribosyltransferase,IMP Pyrophosphorylase,HGPRT,HPRTase,Hypoxanthine Guanine Phosphoribosyltransferase,Phosphoribosyltransferase, Guanine,Phosphoribosyltransferase, Hypoxanthine,Phosphoribosyltransferase, Hypoxanthine-Guanine,Pyrophosphorylase, IMP
D007365 Intercellular Junctions Direct contact of a cell with a neighboring cell. Most such junctions are too small to be resolved by light microscopy, but they can be visualized by conventional or freeze-fracture electron microscopy, both of which show that the interacting CELL MEMBRANE and often the underlying CYTOPLASM and the intervening EXTRACELLULAR SPACE are highly specialized in these regions. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p792) Cell Junctions,Cell Junction,Intercellular Junction,Junction, Cell,Junction, Intercellular,Junctions, Cell,Junctions, Intercellular
D007621 Karyotyping Mapping of the KARYOTYPE of a cell. Karyotype Analysis Methods,Analysis Method, Karyotype,Analysis Methods, Karyotype,Karyotype Analysis Method,Karyotypings,Method, Karyotype Analysis,Methods, Karyotype Analysis
D010703 Phorbol Esters Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. Phorbol Diester,Phorbol Ester,Phorbol Diesters,Diester, Phorbol,Diesters, Phorbol,Ester, Phorbol,Esters, Phorbol
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001681 Biological Assay A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. Bioassay,Assay, Biological,Assays, Biological,Biologic Assay,Biologic Assays,Assay, Biologic,Assays, Biologic,Bioassays,Biological Assays
D013724 Teratoma A true neoplasm composed of a number of different types of tissue, none of which is native to the area in which it occurs. It is composed of tissues that are derived from three germinal layers, the endoderm, mesoderm, and ectoderm. They are classified histologically as mature (benign) or immature (malignant). (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1642) Dysembryoma,Teratoid Tumor,Teratoma, Cystic,Teratoma, Mature,Teratoma, Benign,Teratoma, Immature,Teratoma, Malignant,Benign Teratoma,Benign Teratomas,Dysembryomas,Immature Teratoma,Immature Teratomas,Malignant Teratoma,Malignant Teratomas,Teratoid Tumors,Teratomas,Teratomas, Benign,Teratomas, Immature,Teratomas, Malignant,Tumor, Teratoid,Tumors, Teratoid
D013729 Terpenes A class of compounds composed of repeating 5-carbon units of HEMITERPENES. Isoprenoid,Terpene,Terpenoid,Isoprenoids,Terpenoids

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