Page 281 - 2014 Printable Abstract Book
P. 281
(PS4-79) Radiation-induced necrosis in glioblastoma multiforme compared to normal human
astrocytes. Linda S. Yasui; Kati Owens, MS; Miranda Foster; and Whitney Miter, Northern Illinois
University, DeKalb, IL
When brain tumors are treated with radiation therapy, a risk of radiation-induced necrosis of
healthy brain tissue always exists. Insidious and potentially fatal, radiation necrosis of the brain may
develop months or even years after irradiation. It is reasonable to expect a release of danger signals from
cells undergoing cellular necrosis and that these released danger signals provide the initial stimulus for an
inflammatory cascade leading to the tissue response, also termed necrosis. Therefore, to identify the
cellular source of the necrosis inducing danger signals, radiation-induced cellular necrosis was
investigated in glioblastoma multiforme (GBM) or normal human astrocyte (NHA) cells irradiated with
gamma radiation. Evidence for cellular necrosis was provided by transmission electron microscopy (TEM)
of cells imaged at 3 or 7 days after irradiation. TEM images of irradiated U251 cells shows a reduced
percentage of GBM cells undergoing necroptosis after treatment with 5 µM necrostatin plus 10 Gy gamma
irradiation compared to U251 cells treated with 10 Gy gamma radiation alone. Therefore, necrostatin
treatment rescued irradiated U251 cells from necrosis. In contrast, no necrotic irradiated NHA cells were
observed, even 7 days after irradiation. The lack of detectable necrosis at 7 days after 10 Gy gamma
irradiation in NHA cells indicates that only irradiated GBM cells can provide the initial release of danger
signals for radiation necrosis. Reduction in levels of high mobility group box 1 (HMGB1) from irradiated
GBM cells measured by western blotting confirms the idea of a release of danger signals in irradiated GBM
cells. Ongoing flow cytometry studies of annexin-PI stained GBM cells confirm necrosis induction by
gamma irradiation and our suppression of necrosis by necrostatin data. The standard practice of surgical
resection of GBM tumor before radiation therapy is supported by our hypothesis of necrosing GBM cells
providing the initial stimulus or signal for tissue level radiation necrosis.
(PS4-80) Metabolic effects of sublethal exposure to ionizing radiation. Charles Mitz; Chris Thome; Mary
Ellen Cybulski; Joanna Y. Wilson; and Douglas R. Boreham, McMaster University, Hamilton, Canada
Growth/metabolic effects resulting from low dose and low dose rate irradiation are often
substantially different from those that would be predicted at higher exposures. This non-linearity is
thought to be related to stress response mechanisms that include expression of heat shock proteins (HSPs)
that protect DNA from damage or facilitate its repair. The need for environmental conditions to trigger
the stress response requires there to be a trade-off between observed beneficial effects and some form
of evolutionarily relevant cost. We investigated the metabolic effects of single acute and fractionated
doses of 662 keV gamma radiation (0.1 to 60 Gy) on developing Lake Whitefish embryos to determine the
effects on hatch timing, growth, and metabolic efficiency measured as yolk conversion efficiency (YCE).
Samples were collected in a 2, 8, 32, and 110 hr time series following irradiation andanalyzed to quantify
HSP gene and protein expression using RT-qPCR and western blotting techniques. The question of interest
is whether sublethally stressed embryos will exhibit a trade-off between increased stress tolerance and
growth/YCE. A secondary question is whether the metabolic cost of the stress response mechanisms can
be measured independently from the associated stress.
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astrocytes. Linda S. Yasui; Kati Owens, MS; Miranda Foster; and Whitney Miter, Northern Illinois
University, DeKalb, IL
When brain tumors are treated with radiation therapy, a risk of radiation-induced necrosis of
healthy brain tissue always exists. Insidious and potentially fatal, radiation necrosis of the brain may
develop months or even years after irradiation. It is reasonable to expect a release of danger signals from
cells undergoing cellular necrosis and that these released danger signals provide the initial stimulus for an
inflammatory cascade leading to the tissue response, also termed necrosis. Therefore, to identify the
cellular source of the necrosis inducing danger signals, radiation-induced cellular necrosis was
investigated in glioblastoma multiforme (GBM) or normal human astrocyte (NHA) cells irradiated with
gamma radiation. Evidence for cellular necrosis was provided by transmission electron microscopy (TEM)
of cells imaged at 3 or 7 days after irradiation. TEM images of irradiated U251 cells shows a reduced
percentage of GBM cells undergoing necroptosis after treatment with 5 µM necrostatin plus 10 Gy gamma
irradiation compared to U251 cells treated with 10 Gy gamma radiation alone. Therefore, necrostatin
treatment rescued irradiated U251 cells from necrosis. In contrast, no necrotic irradiated NHA cells were
observed, even 7 days after irradiation. The lack of detectable necrosis at 7 days after 10 Gy gamma
irradiation in NHA cells indicates that only irradiated GBM cells can provide the initial release of danger
signals for radiation necrosis. Reduction in levels of high mobility group box 1 (HMGB1) from irradiated
GBM cells measured by western blotting confirms the idea of a release of danger signals in irradiated GBM
cells. Ongoing flow cytometry studies of annexin-PI stained GBM cells confirm necrosis induction by
gamma irradiation and our suppression of necrosis by necrostatin data. The standard practice of surgical
resection of GBM tumor before radiation therapy is supported by our hypothesis of necrosing GBM cells
providing the initial stimulus or signal for tissue level radiation necrosis.
(PS4-80) Metabolic effects of sublethal exposure to ionizing radiation. Charles Mitz; Chris Thome; Mary
Ellen Cybulski; Joanna Y. Wilson; and Douglas R. Boreham, McMaster University, Hamilton, Canada
Growth/metabolic effects resulting from low dose and low dose rate irradiation are often
substantially different from those that would be predicted at higher exposures. This non-linearity is
thought to be related to stress response mechanisms that include expression of heat shock proteins (HSPs)
that protect DNA from damage or facilitate its repair. The need for environmental conditions to trigger
the stress response requires there to be a trade-off between observed beneficial effects and some form
of evolutionarily relevant cost. We investigated the metabolic effects of single acute and fractionated
doses of 662 keV gamma radiation (0.1 to 60 Gy) on developing Lake Whitefish embryos to determine the
effects on hatch timing, growth, and metabolic efficiency measured as yolk conversion efficiency (YCE).
Samples were collected in a 2, 8, 32, and 110 hr time series following irradiation andanalyzed to quantify
HSP gene and protein expression using RT-qPCR and western blotting techniques. The question of interest
is whether sublethally stressed embryos will exhibit a trade-off between increased stress tolerance and
growth/YCE. A secondary question is whether the metabolic cost of the stress response mechanisms can
be measured independently from the associated stress.
279 | P a g e
