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(PP300) Incubation of 32D cl 3 factor-dependent hematopoietic cells in ethyl pyruvate (EP) increases radiation resistance.
Epperly, Michael*,1, Fink, Mitchell2, Hricisak, Lauren1, Zhang, Xichen1, Greenberger, Joel1, 1 Radiation Oncology, Pittsburgh, PA, USA2 Critical Care Medicine, Pittsburgh, PA, USA
ABSTRACT- Ethyl pyruvate (EP) is a stable lipophilic derivative shown to protect animals from ischemia/perfusion-induced injury. EP inhibits the release of TNF and high mobility group B1, pro-inflammatory cytokines. EP also attenuates the activation of both p38 mitogen activated protein kinase (MAPK) and NFK signaling pathways. Since these cytokines and pathways are involved in irradiation sensitivity, we investigated whether EP protects cells in vitro. Cells from the 32D cl 3 cell line were incubated: 1) in the absence of EP, 2) in the presence of EP 1 hour before irradiation, 3) in the absence of EP with EP added following irradiation, or 4) in the presence of EP 1 hour before irradiation and following irradiation. 32D cl 3 cells incubated in the presence of EP 1 hour before irradiation and plated in methylcellulose containing EP had an increased D0 compared to 32D cells alone (2.20 ± 0.25, 2.1 ± 0.15, and 1.84 ± 0.25 Gy, respectively). However, there was no change in the shoulder of the survival curve for these conditions (n=2.00 ± 1.01, 1.11 ± 0.12, or 1.70 ± 0.37, respectively). Incubating 32D cl cells in the presence of EP before and following irradiation resulted in an increased shoulder on the survival curve compared to untreated, irradiated 32D cl 3 cells (n=4.14 ± 1.59 and 1.70 ± 0.6, respectively, p = 0.0485). To determine whether EP inhibits apoptosis following irradiation, 32D cl 3 cells were incubated in either the absence or presence of EP for 1 hour and irradiated to 10 Gy. 32D cl 3 cells incubated in EP for 24 hours before irradiation had 2.8 ± 0.7% apoptotic cells compared to 23.7 ± 1.8% for 32D cl 3 cells irradiated in the absence of EP. The data indicate that EP is an effective radioprotector.
Key words: Ethyl pyruvate, radioprotection, NFKbeta
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