Selective toxicity of 6-hydroxydopamine and ascorbate for human neuroblastoma in vitro: a model for clearing marrow prior to autologous transplant.
6-Hydroxydopamine (6-OHDA) is a neurotoxin for catecholaminergic neurons and neuroblasts. Since frequent marrow involvement in neuroblastoma restricts the exploitation of stored autologous bone marrow for rescue postchemotherapy, the potential for tumor-specific in vitro specificity of 6-OHDA was studied. The cytotoxic effect of 6-OHDA on 12 human neuroblastoma cell lines was compared to the effect on nonneuroblastoma cell lines. Most neuroblastoma cell lines were very sensitive to 6-OHDA (average concentration killing 50% of cells, 22 microgram/ml; range, 2.8 to 65.4). Cells derived from catecholamine-producing tumors were more sensitive to 6-OHDA than were those from non-catecholamine producers. By contrast, human fibroblasts, lymphoblastoid cell lines, and normal marrow were relatively insensitive to 6-OHDA; the concentration needed to kill 50% of cells for most of these cells exceeded 100 microgram/ml. Leukemia cell lines and a rhabdomyosarcoma cell line were intermediate in sensitivity. Ascorbate and 6-OHDA were synergistic in toxicity for human neuroblastoma cells. Thus, in vitro addition of 6-OHDA and ascorbate was rapidly lethal for human neuroblastoma cells at concentrations which were minimally toxic for hematopoietic cells. This differential toxicity provides a possible means for selective destruction of neuroblastoma cells in bone marrow harvested for autologous transplantation.
D001205:Ascorbic Acid / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects*; D016026:Bone Marrow Transplantation; D002395:Catecholamines / Q000652:urine; D002460:Cell Line; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology* / Q000633:toxicity; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D014182:Transplantation, Autologous
D002395:Catecholamines; D006892:Hydroxydopamines; D001205:Ascorbic Acid