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.