The Journal of Experimental Medicine · 1992 · 218 citations · 30 references
Life SciencesCell BiologyMolecular BiologyApoptosisChemotherapyDna RepairApoptosis RegulationApoptosis ResistanceApoptotic SignalingCell DeathDna DamageDna Damage-induced ApoptosisApoptosis After IrradiationApoptosis-related Dna DamageBone Marrow - Derived CellsCytokine-mediated ApoptosisDna CleavageDna Damage ResponsesDna Damage-induced Cell DeathDouble-strand Dna Breaks
Murine bone marrow-derived cells, dependent on interleukin 3 (IL-3) for their growth in culture, undergo programmed cell, or apoptosis, upon cytokine withdrawal. Here it is reported that a variety of DNA damaging agents cause a more rapid onset of apoptosis in a factor-dependent cell line, BAF3, deprived of IL-3. In contrast, when cultured in the presence of IL-3, or other growth promoting factors, BAF3 cells are highly resistant to X-irradiation and the cytotoxic drugs etoposide and cisplatin. Overexpression of the bcl2 gene product also protects BAF3 cells from DNA damage. The presence of IL-3 is not required during the initial events of DNA damage or its repair. In the absence of IL-3, cells still complete the repair of DNA breaks within 15 min, and continue to cycle for 5 h. At this time, IL-3 is necessary to prevent the accelerated onset of DNA cleavage from a G2 arrest point.
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Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
David M. Hockenbery, Gabriel Núñez, Curt Milliman et al. · Nature · 1990 · 3.8K citations
bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes
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