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Selective Toxicity of 6-Hydroxydopamine and Ascorbate for Human Neuroblastoma in Vitro: A Model for Clearing Marrow Prior to Autologous Transplant¹

Department of Internal Medicine, Division of Hematology and Oncology, Evelyn L. Overton Memorial Laboratories for Hematology and Oncology Research, and the Cancer Center, University of Texas Health Science Center, Dallas, Texas 75235

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 (average concentration killing 50% of cells, 22 µg/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 µg/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.

¹ This work was supported by NIH Grants CA23115 and CA18132 from the National Cancer Institute, Grant CH-59 from the American Cancer Society, the Southwestern Medical Foundation-Kinsler Williamson Brown Fund, and the Meadows Foundation.

² Present address: Division Surgeon's Office, 3rd Marine Division, FMF FPO San Francisco, Calif. 96602.

³ Scholar of the Leukemia Society of America. To whom for reprints requests should be sent, at Cancer Center, University of Texas Health Science Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235.

Received 9/ 9/81. Accepted 12/ 9/81.