The role of reactive oxygen compounds derived from 6-hydroxydopamine for bone marrow purging from neuroblastoma cells.
6-Hydroxydopamine(6-OHDA), a specific neurotoxin against sympathetic nerve cells, is a drug already used for purging of bone marrow from neuroblastoma cells before autologous bone marrow transplantation. However, we could not detect significant differences in the toxicity of 6-OHDA against neuroblastoma and other tumor cells under the purging conditions clinically used. In contrast, bone marrow stem cells were much more resistant. The unspecific toxic effect of 6-OHDA is caused by H2O2 or H2O2-derived products which are generated by auto-oxidation in the incubation medium before a significant amount of 6-OHDA is taken up by the cells. Withdrawal of oxygen during the incubation period and subsequent incubation with an oxygen containing medium led to a more specific destruction of neuroblastoma cells which can take up 6-OHDA selectively.
Bruchelt
G
G
Buck
J
J
Girgert
R
R
Treuner
J
J
Niethammer
D
D
D001205:Ascorbic Acid / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects*; D002374:Catalase; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004227:Dithionite / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D006892:Hydroxydopamines / Q000633:toxicity*; D009447:Neuroblastoma / Q000188:drug therapy*; D010100:Oxygen / Q000633:toxicity; D013482:Superoxide Dismutase; D013481:Superoxides / Q000633:toxicity
D006892:Hydroxydopamines; D013481:Superoxides; D004227:Dithionite; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; D010100:Oxygen