Malik Z, Djaldetti M
Department of Medicine "B" and Hematology Laboratory, Hasharon Hospital, Petah-Tiqva, Israel.
Exp Hematol. 1980 Aug;8(7):867-79.
Hemin and protoporphyrin exerted a cytotoxic effect on lymphocytes from 24 patients with chronic lymphocytic leukemia (CLL). The porphyrins inhibited protein and RNA synthesis in a dose dependent pattern. Exposure of leukemic cells to 15 microM hemin for 10 min reduced leucine incorporation to less than 20%, and 78% of the cells were freely permeable to trypan blue. Hemin at 0.17 microM had to be bound to 10(6) cells in the dark to produce this killing effect. On the other hand, the control lymphocytes from 20 healthy subjects were relatively resistant to the hemin effect, and cell damage was reversible. Fetal calf serum (FCS) protected most leukemic lymphocytes from prophyrin toxicity. The combination of human hemoglobin with free protoporphyrin showed a synergistic toxicity, and this combination was the most potent inhibitor of protein synthesis in the presence of serum. 55Fe-hemin was preferentially bound to leukemic lymphocytes, and the binding site of protoporphyrin was observed to be on the cell surface membrane. The hemin quenching effect of diphenyl hexatriene (DPH) stained cell fluorescence indicated that hemin was apparently bound to the lipid layer of the outer membrane. Scanning electron microscopy (SEM) of hemin treated cells revealed an initial development of membranal blebs, followed by total destruction of the cell surface membrane. Transmission electron microscopy (TEM) of the treated cells showed a profound damage in the cytoplasma and nucleus. Control lymphocytes treated by hemin appeared relatively undamaged and free of membranal blebs.
氯高铁血红素和原卟啉对24例慢性淋巴细胞白血病（CLL）患者的淋巴细胞具有细胞毒性作用。卟啉以剂量依赖性方式抑制蛋白质和RNA合成。将白血病细胞暴露于15微摩尔氯高铁血红素中10分钟，亮氨酸掺入量减少至不到20%，并且78%的细胞可自由透过台盼蓝。0.17微摩尔的氯高铁血红素必须在黑暗中与10⁶个细胞结合才能产生这种杀伤作用。另一方面，来自20名健康受试者的对照淋巴细胞对氯高铁血红素的作用相对耐药，并且细胞损伤是可逆的。胎牛血清（FCS）可保护大多数白血病淋巴细胞免受卟啉毒性影响。人血红蛋白与游离原卟啉的组合显示出协同毒性，并且在有血清存在的情况下，这种组合是最有效的蛋白质合成抑制剂。⁵⁵Fe - 氯高铁血红素优先与白血病淋巴细胞结合，并且观察到原卟啉的结合位点位于细胞表面膜上。二苯基己三烯（DPH）染色细胞荧光的氯高铁血红素猝灭效应表明，氯高铁血红素显然与外膜的脂质层结合。氯高铁血红素处理细胞的扫描电子显微镜（SEM）显示最初出现膜泡，随后细胞表面膜完全破坏。处理细胞的透射电子显微镜（TEM）显示细胞质和细胞核有严重损伤。经氯高铁血红素处理的对照淋巴细胞似乎相对未受损且没有膜泡。
