Measurement of doxorubicin-induced lipid peroxidation under the conditions that determine cytotoxicity in cultured tumor cells.
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.
Benchekroun
M N
MN
Fondation Bergonié, Bordeaux, France.
Robert
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism*; D051381:Rats; D013858:Thiobarbiturates / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D013858:Thiobarbiturates; D008315:Malondialdehyde; D004317:Doxorubicin; C029684:thiobarbituric acid