bcl-2 delay of alkylating agent-induced apoptotic death in a murine hemopoietic stem cell line.
Many cytotoxic agents kill cells by invoking a specific death pathway termed physiological cell death, or apoptosis. Treatment of a murine hemopoietic stem cell line, FDCP-mix, with methylmethanesulfonate (MMS) or N'-methyl-N'-nitrosourea (MNU) leads to death by apoptosis. Retroviral gene transfer was used to overexpress the bcl-2 oncogene in FDCP-mix cells, and this was associated with a delay in apoptosis in these cells after treatment with MNU and MMS and decreased sensitivity of colony formation to the cytotoxic effects of MMS. These data suggest an explanation for the refractory nature of bcl-2-expressing follicular lymphoma to cytotoxic chemotherapy and furthermore suggest that DNA-damaging antitumor therapy may contribute to the progression of disease.
Fairbairn
L J
LJ
CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Cowling
G J
GJ
Dexter
T M
TM
Rafferty
J A
JA
Margison
G P
GP
Reipert
B
B
D000818:Animals; D017209:Apoptosis; D004260:DNA Repair; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D066298:In Vitro Techniques; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D008770:Methylnitrosourea; D008741:Methyl Methanesulfonate