Very high cytotoxicity of bleomycin introduced into the cytosol of cells in culture
| Autor: | Lluis M. Mir, B. Poddevin, Jean Belehradek, Stéphane Orlowski |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cell Membrane Permeability Cell Survival Stereochemistry Cell Biology Biochemistry Bleomycin Cricetulus Cytosol Electricity In vivo Cricetinae medicine Animals Cytotoxic T cell Trypsin Cytotoxicity Cells Cultured Pharmacology Dose-Response Relationship Drug urogenital system Electroporation nutritional and metabolic diseases Isoquinolines In vitro medicine.anatomical_structure Cell culture Biophysics |
| Zdroj: | Biochemical Pharmacology. 42:S67-S75 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(91)90394-k |
| Popis: | We observed previously in vitro that the cytotoxicity of bleomycin (BLM), an anticancer drug in current use, was greatly potentiated by exposing cultured cells to appropriately chosen electric pulses. We then showed in vivo, on tumor-bearing mice, that the same electric pulses also potentiated the antitumoral activity of BLM. In the present work, we demonstrate on DC-3F cells in vitro, that this potentiation is closely related to cell electropermeabilization and the consequent direct internalization of BLM molecules in the cytosol. The survival response curve (SRC) of the electropermeabilized (EP) cells exposed to BLM (plotted as logarithm of survival versus external drug concentration) shows a linear pattern usual for the SRCs of intact cells exposed to current cytotoxic drugs, though in the nanomolar range of concentrations. We have succeeded in determining the relation between BLM cytotoxicity on EP cells and the number of electroloaded BLM molecules per cell (that is the average number, per cell, of BLM molecules internalized into the cytosol). We conclude that (1) BLM molecules possess very intense cytotoxic activity which in non-EP cells is drastically limited by the intact plasma membrane; and (2) in these intact cells, the plasma membrane is responsible for the unusual upward concave curvature of the SRC resulting from exposure to BLM. |
| Databáze: | OpenAIRE |
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