Increased generation of lipid-derived and ascorbate free radicals by L1210 cells exposed to the ether lipid edelfosine.
Using the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, we have detected a lipid-derived carbon-centered free radical generated from intact L1210 lymphoblastic leukemia cells that were exposed to 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (edelfosine or ET-18-OCH3) and oxidative stress. The spectral characteristics, including hyperfine splitting constants of aN = 15.61G and aH = 2.65G, were consistent with the spin trapping of an alkyl radical. Radical detection required iron and prior enrichment of cellular components with the polyunsaturated fatty acid docosahexaenoic acid; unmodified cells failed to generate detectable free radical. Ascorbate further enhanced radical generation. The detection of lipid-derived free radicals when intact cells are exposed to edelfosine provides further evidence that oxidative stress may play an important role in the cytotoxic mechanism of this class of anticancer drug.
Wagner
B A
BA
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
Buettner
G R
GR
Burns
C P
CP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D007501:Iron / Q000494:pharmacology; D007939:Leukemia L1210 / Q000378:metabolism*; D015227:Lipid Peroxidation; D009589:Nitrogen Oxides; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011725:Pyridines; D013113:Spin Labels
D000970:Antineoplastic Agents; D005609:Free Radicals; D009589:Nitrogen Oxides; D010742:Phospholipid Ethers; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; C026659:edelfosine; D004281:Docosahexaenoic Acids; D007501:Iron; D001205:Ascorbic Acid