Analysis of cellular heterogeneity in the response of human leukemic cells to photosensitization induced by pyrene-containing fatty acid.
Incubation of cells with 12-(1-pyrene) dodecanoic acid (P12) followed by irradiation with ultraviolet light at 366 nm (UVA) resulted in cytotoxicity. We compared the photosensitivity to UVA irradiation of various human myelo-monocytic leukemic cell lines, their intra- and inter-clonal variability and correlated their photosensitivity to P12-uptake and metabolism. The fluorescence properties of pyrene were utilized for flow cytometric analysis of cell distribution with respect to P12-uptake as well as for sorting subpopulations differing in their fluorescence. Spectrofluorometric analysis of the total cell-associated fluorescence and of the cellular lipids-associated fluorescence were also carried out. Considerable heterogeneity in P12-uptake and photosensitivity was found not only among cell lines, but also in the response of different clones and among the individual cells in specific clonal populations. Within a clone, photosensitivity was related to the amount of P12 taken up by the individual cells, while among different cell lines and their clones the photosensitivity was correlated with the proportion of cellular pyrene-linked phospholipids. The larger the fraction of pyrene-linked phospholipids within the cell--the more sensitive it was to UVA-irradiation. Photosensitivity could be affected by changing the proportion of cellular pyrene-linked phospholipids. Cells treated with cAMP showed an increase in total P12-uptake, but the proportion of pyrene-linked phospholipids was reduced, resulting in lower photosensitivity. These findings, demonstrating that by manipulating lipid metabolism photosensitivity can be modified, may prove useful in a clinical setting for selective photosensitization of malignant cells.
Fibach
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E
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Rachmilewitz
E A
EA
Gatt
S
S
D002470:Cell Survival / Q000528:radiation effects; D000242:Cyclic AMP / Q000494:pharmacology; D006801:Humans; D007850:Lauric Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology*; D008027:Light; D010743:Phospholipids / Q000378:metabolism; D010778:Photochemotherapy; D012542:Scattering, Radiation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007850:Lauric Acids; D010743:Phospholipids; C040596:12-(1-pyrene)dodecanoic acid; D000242:Cyclic AMP