Fibach E, Rachmilewitz E A, Gatt S
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Leuk Res. 1989;13(12):1099-104. doi: 10.1016/0145-2126(89)90155-0.
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.
用12-(1-芘基)十二烷酸（P12）处理细胞，随后用366nm的紫外线（UVA）照射，会导致细胞毒性。我们比较了各种人类骨髓单核细胞白血病细胞系对UVA照射的光敏性、它们的克隆内和克隆间变异性，并将它们的光敏性与P12摄取和代谢相关联。利用芘的荧光特性对细胞关于P12摄取的分布进行流式细胞术分析，以及对荧光不同的亚群进行分选。还进行了全细胞相关荧光和细胞脂质相关荧光的分光荧光分析。结果发现，不仅在细胞系之间，而且在不同克隆的反应以及特定克隆群体中的单个细胞之间，P12摄取和光敏性都存在相当大的异质性。在一个克隆内，光敏性与单个细胞摄取的P12量相关，而在不同细胞系及其克隆之间，光敏性与细胞芘连接的磷脂比例相关。细胞内芘连接的磷脂比例越大，其对UVA照射就越敏感。改变细胞芘连接的磷脂比例可能会影响光敏性。用cAMP处理的细胞显示总P12摄取增加，但芘连接的磷脂比例降低，导致光敏性降低。这些发现表明通过操纵脂质代谢可以改变光敏性，这在临床环境中对恶性细胞的选择性光致敏可能是有用的。
