Involvement of membrane bleomycin-binding sites in bleomycin cytotoxicity
| Autor: | Lluis M. Mir, Géraldine Pron, Jean Belehradek, Stéphane Orlowski |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities media_common.quotation_subject Cell Mutant Drug Resistance Biology Biochemistry Bleomycin Cricetulus Cricetinae medicine Animals Cytotoxicity Internalization media_common Cell Line Transformed Pharmacology Genetics Binding Sites urogenital system Electroporation Cell Membrane nutritional and metabolic diseases Transfection Molecular biology In vitro medicine.anatomical_structure Cell culture Mutation Carrier Proteins |
| Zdroj: | Biochemical pharmacology. 48(2) |
| ISSN: | 0006-2952 |
| Popis: | The authors have recently shown the existence of bleomycin (BLM)-binding sites at the surface of DC-3F cells. In order to study the involvement of these sites in the sensitivity of the cells to bleomycin several BLM-resistant cell lines from DC-3F cells were analysed. These mutants were obtained by electrotransfection of the Sh ble gene (D/BlmI cells) or the Sh ble-βGal fusion gene (D/BlmII cells) and/or by continuous culture in the presence of BLM (D/BlmIR and D/Blm40 cells). The resistance levels of the D/BlmII and D/Blm40 cells were 50- and 22-fold, respectively, determined at the ec 50 level. The D/BlmI cells were only 2-fold resistant, whereas D/BlmIR cells were so resistant that almost no cytotoxicity was detected up to 200 μm BLM external concentration. Electropermeabilization was used in an attempt to bypass the plasma membrane of the cells and permit the distinction between internal resistance and membrane resistance. The former was observed when the products of the transfected genes were present. With respect to membrane resistance, differences were detected in the number of BLM-binding sites in several mutant cell lines, which could account for the differences in cell sensitivity to BLM. This suggests that the BLM-binding sites found at the cell surface may play a crucial role in BLM internalization and consequently in its cytotoxicity. |
| Databáze: | OpenAIRE |
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