Article

Interleukin 3 protects murine bone marrow cells from apoptosis induced by DNA damaging agents

Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
Journal of Experimental Medicine (Impact Factor: 12.52). 11/1992; 176(4):1043-51.
Source: PubMed

ABSTRACT

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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Available from: Jacqueline Marvel
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    • "For example, IL-6 has been shown to protect myeloid cells from apoptosis that is induced by a temperature-sensitive mutant of p53 (YonishRouach et al., 1991). Similarly, in BAF-3 cells, IL-3 stimulation has been shown to prevent p53-induced apoptosis but not cell cycle arrest upon c-irradiation (Canman et al., 1995; Collins et al., 1992). Furthermore, constitutively active PI3K or AKT have been shown to slow down the rate of p53-mediated apoptosis (Sabbatini and McCormick, 1999). "
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    • "BAF3 cells resisted X-ray-and cytotoxin-induced injury when the culture media was supplemented with IL-3. Treatment with IL-3 exerted no apparent effect on early-stage DNA damage and repair , but played an essential role in preventing the acceleration of DNA fragmentation at the G2 phase block point [15] . In addition, IL-3 can accelerate G2/M phase arrest and prevent apoptosis of mouse hematopoietic progenitor 32D and human UT7 cell lines in response to etoposide, a type II topoisomerase inhibitor [18]. "
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    • "The first two populations were cultured in IL-3 containing media prior to factor withdrawal. As reported previously, removal of IL-3 from control Ba/F3 cells results in loss of cell viability that begins within 24 h after factor withdrawal. (28) Removal of IL-3 from stably transfected cells also resulted in cell death with similar kinetics as control cells. CID withdrawal from CID-selected cells reversed proliferation and resulted in cell death. "
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