SELECTIVE TOXICITY OF 6-HYDROXYDOPAMINE AND ASCORBATE FOR HUMAN NEURO-BLASTOMA INVITRO - A MODEL FOR CLEARING MARROW PRIOR TO AUTOLOGOUS TRANSPLANT

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (4) , 1331-1336
Abstract
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 toxicity 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 (LC50, 22 .mu.g/ml; range, 2.8-65.4). Cells derived from catecholamine-producing tumors were more sensitive to 6-OHDA than were those from noncatecholamine producers. By contrast, human fibroblasts, lymphoblastoid cell lines and normal marrow were relatively insensitive to 6-OHDA; the LC50 for most of these cells exceeded 100 .mu.g/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.

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