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Measurement of doxorubicin-induced lipid peroxidation under the conditions that determine cytotoxicity in cultured tumor cells

✍ Scribed by M. Nabil Benchekroun; Jacques Robert


Publisher
Elsevier Science
Year
1992
Tongue
English
Weight
468 KB
Volume
201
Category
Article
ISSN
0003-2697

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✦ Synopsis


We have investigated doxorubicin-induced lipid peroxidation by the measure of malondialdehyde (MDA) formation in rat glioblastoma cells and human breast carcinoma cells in culture. There was a significant production of MDA when the cells were incubated with pharmacologically relevant doxorubicin concentrations, i.e., concentrations that produce a significant cytotoxicity (0.1 micrograms/ml). At equitoxic doses, vincristine provided no lipid peroxidation, indicating that MDA formation is not a consequence of cell death. Doxorubicin-induced lipid peroxidation was maximal 24 h after incubation of the cells with doxorubicin, indicating that a delay was necessary for the free radical-mediated membrane damage induced by doxorubicin. In the presence of alpha-tocopherol in the culture medium, the doxorubicin-induced MDA formation was inhibited. The development of this method will help in defining the role of free radicals and lipid peroxidation in the cytotoxicity of doxorubicin.


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## Methods Mitoxantrone was purchased from Lederle (France) and doxorubicin from Dakota (France). Stock solutions stored at Ϫ20°C (9 ϫ 10 Ϫ4 M for doxorubicin and 4 ϫ 10 Ϫ3 M for mitoxantrone) and dilutions of doxorubicin and mitoxantrone were freshly prepared in physiological saline solution, NaC