Merocyanine 540 mediated photolysis of normal bone marrow, committed hemopoietic progenitors and neoplastic cells. implications for bone marrow purging.
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.
Lydaki
E
E
Department of Ped Hematology-Oncology, University of Crete Medical School, Heraklio, Greece.
Dimitriou
H
H
Papazoglou
T
T
Liu
W Q
WQ
Kalmanti
M
M
D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D002648:Child; D004307:Dose-Response Relationship, Radiation; D018922:HL-60 Cells / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007834:Lasers; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D009447:Neuroblastoma / Q000473:pathology; D010782:Photolysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D011744:Pyrimidinones / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011744:Pyrimidinones; D011838:Radiation-Sensitizing Agents; C003954:merocyanine dye