title: Singlet oxygen toxicity is cell line-dependent: a study of lipid peroxidation in nine leukemia cell lines.
abstract: Singlet oxygen (1O2) can be quenched by water, lipids, proteins, nucleic acids and other small molecules. Polyunsaturated fatty acids (PUFA) of cells principally quench 1O2 by chemical mechanisms, producing lipid hydroperoxides, while proteins physically and chemically quench 1O2. Because cell lines can have different PUFA and protein levels, we hypothesized that 1O2 toxicity will vary between cell lines. We used Photofrin as a source of 1O2. Exposure of nine different leukemia cell lines (CEM, HEL, HL-60, K-562, KG-1, L1210, Molt-4, THP-1 and U-937) to Photofrin and light results in changes in membrane permeability (trypan blue) that vary with cell line. The greater the lipid content of the cell line, the less susceptible they are to membrane damage. When the cell media was supplemented with docosahexaenoic acid (DHA, 22:6), the overall unsaturation of cellular lipids increased. Photofrin and light resulted in increased radical formation in these supplemented cells compared to controls; however, there was no difference in membrane permeability between DHA-supplemented and control cells. Lipid-derived radical formation (electron paramagnetic resonance spin trapping) was cell line dependent; but no correlation between lipid content of cells and radical formation was found. However, we found that the greater the protein content of cells the more they were protected against membrane damage induced by Photofrin photosensitization. This suggests that cellular proteins are a key target for 1O2-mediated toxicity. A remarkable observation is that cell size correlates inversely with ability of cells to cope with a given flux of 1O2.
authors.affiliation: Free Radical Research Institute & ESR Facility, University of Iowa, Iowa City 52242-1101, USA. freya-schafer@uiowa.edu
authors.forename: F Q
authors.initials: FQ
authors.lastname: Schafer
authors.forename: G R
authors.initials: GR
authors.lastname: Buettner
mesh_terms: D000818:Animals; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D051379:Mice; D010100:Oxygen / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D010100:Oxygen