Studies with cytotoxic agents suggest that apoptosis is not a major determinant of clonogenic death in neuroblastoma cells.
We have previously reported the selection of a radioresistant human neuroblastoma cell line, Clone F, from IMR32 cells. We have shown that clonogenic radioresistance in these cells is accompanied by a reduced level of radiation-induced apoptosis [Cancer Res 55 (1995) 4915]. Here, we measured the response of these lines to several cytotoxic agents, in terms of clonogenicity and apoptosis. In the clonogenic assay, the radioresistant line was also resistant to cisplatin, melphalan and doxorubicin, but not to perillyl alcohol. However, all these agents produced less apoptosis in the Clone F cells, except cisplatin, which failed to induce any apoptosis in either cell line. Reduced apoptosis cannot be the cause of the Clone F cells' resistance to cisplatin. By extension, the Clone F cells' resistance to radiation and other agents cannot be due to diminished apoptosis either. Based on these results, apoptosis may not be a useful surrogate for clonogenic outcome.
Russell
J
J
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, K210 425 E68th Street, New York, NY 10021, USA. russellj@mskcc.org
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D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D019254:Genes, bcl-2; D006801:Humans; D008558:Melphalan / Q000627:therapeutic use; D039821:Monoterpenes / Q000627:therapeutic use; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D011836:Radiation Tolerance; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D039821:Monoterpenes; C032208:perillyl alcohol; D004317:Doxorubicin; D002945:Cisplatin; D008558:Melphalan