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部花青540介导的正常骨髓、定向造血祖细胞和肿瘤细胞的光解作用。对骨髓净化的意义。

Merocyanine 540 mediated photolysis of normal bone marrow, committed hemopoietic progenitors and neoplastic cells. implications for bone marrow purging.

作者信息

Lydaki E, Dimitriou H, Papazoglou T, Liu W Q, Kalmanti M

机构信息

Department of Ped Hematology-Oncology, University of Crete Medical School, Heraklio, Greece.

出版信息

Leuk Res. 1997 Jul;21(7):641-50. doi: 10.1016/s0145-2126(97)00023-4.

Abstract

The effect of merocyanine 540 (Mc 540) mediated photoirradiation on both neoplastic and normal hemopoietic progenitor cells was studied. Bone marrow (BM) cells from children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) at initial diagnosis, ALL in remission, neuroblastoma and normal children as well as cells of Reh-6 and HL-60 cell lines were incubated with Mc 540 in the presence of human albumin (HA) and exposed to different argon laser 514 nm doses. Cell survival was estimated using Trypan Blue supravital stain following a 24-h incubation and leukemic cell lines were studied in continuous cell cultures of 4 weeks duration. Our results showed that HA protects normal BM cells from Mc 540 mediated phototoxicity. A 99.9999% inhibition of Reh-6 and HL-60 was noted at irradiation doses where the corresponding mean survival of normal BM cells was 77.4 +/- 12 and 70.3 +/- 10%, respectively. BM leukemic cells from children with ALL and AML were also very sensitive to Mc 540 photoirradiation in contrast to neuroblastoma cells where only a three-fold reduction was observed. Finally, the survival of normal BM progenitors was 38% for colony forming unit erythroid CFU-E, 37% for burst forming unit erythroid BFU-E, 55% for CFU-GM and 29% for CFU-GEMM. In conclusion it seems that Mc 540 mediated photoirradiation in neoplastic cells exerts selective cytotoxicity and can be used in ex vivo purging of malignant cells in BM.

摘要

研究了部花青540(Mc 540)介导的光照射对肿瘤性和正常造血祖细胞的影响。将初诊急性淋巴细胞白血病(ALL)、急性髓细胞白血病(AML)、ALL缓解期、神经母细胞瘤患儿以及正常儿童的骨髓(BM)细胞,连同Reh-6和HL-60细胞系的细胞,在人白蛋白(HA)存在的情况下与Mc 540一起孵育,并暴露于不同剂量的514 nm氩激光下。在24小时孵育后,使用台盼蓝活体染色评估细胞存活率,并在持续4周的细胞培养中研究白血病细胞系。我们的结果表明,HA可保护正常BM细胞免受Mc 540介导的光毒性。在照射剂量下,Reh-6和HL-60的抑制率达到99.9999%,而此时正常BM细胞的相应平均存活率分别为77.4±12%和70.3±10%。与仅观察到三倍减少的神经母细胞瘤细胞相比,ALL和AML患儿的BM白血病细胞对Mc 540光照射也非常敏感。最后,正常BM祖细胞的存活率对于红系集落形成单位(CFU-E)为38%,对于红系爆式集落形成单位(BFU-E)为37%,对于粒-巨噬细胞集落形成单位(CFU-GM)为55%,对于粒-红-巨噬-巨核系集落形成单位(CFU-GEMM)为29%。总之,似乎Mc 540介导的光照射对肿瘤细胞具有选择性细胞毒性,可用于体外清除BM中的恶性细胞。

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