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.This publication has 1 reference indexed in Scilit:
- Enzyme defense against reactive oxygen derivatives. II. Erythrocytes and tumor cellsMolecular and Cellular Biochemistry, 1976