TY - JOUR
T1 - The autophagy-inducing drug carbamazepine is a radiation protector and mitigator
AU - Kim, Hyun
AU - Bernard, Mark E.
AU - Flickinger, John
AU - Epperly, Michael W.
AU - Wang, Hong
AU - Dixon, Tracy M.
AU - Shields, Donna
AU - Houghton, Frank
AU - Zhang, Xichen
AU - Greenberger, Joel S.
N1 - Funding Information:
Supported by the National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) Center for Medical Counter Measures (CMCR) Grant 1U19 A168021 and by NIH T32AG21885.
PY - 2011/10
Y1 - 2011/10
N2 - Purpose: To determine whether Carbamazepine (CBZ) is a radiation protector and/or mitigator. Materials and methods: Murine hematopoietic progenitor 32D cl 3 cells were incubated in 1, 10, or 100 μM CBZ 1 h before or immediately after 08 Gy irradiation and assayed for clonogenic survival. Autophagy was assayed by immunoblot for microtubule-associated protein light chain 3 (LC3). In vivo radioprotection and mitigation were determined with C57BL/6NTac mice. Results: CBZ treatment at 1, 10 or 100 μM for 1 h prior to irradiation increased radioresistance (the dose for 37% survival or D0) from control 1.5 ± 0.1 Gy to 2.1 ± 0.2 Gy (P = 0.012), 2.3 ± 0.1 Gy (P = 0.010), and 3.6 ± 0.7 Gy (P = 0.003), respectively; after irradiation increased the extrapolation number () from 1.5 ± 0.3 to 10.1 ± 4.2 (P = 0.011), 5.5 ± 1.7 (P = 0.019), and 3.6 ± 0.8 (P = 0.014), respectively, and increased autophagy. CBZ treated mice 10 min or 24 h before or 10 min or 12 h after 9.25 Gy total body irradiation (TBI) showed increased survival (P = 0.012, 0.011, 0.0002, and 0.017, respectively). Conclusion: CBZ may be a useful radiation protector and mitigator.
AB - Purpose: To determine whether Carbamazepine (CBZ) is a radiation protector and/or mitigator. Materials and methods: Murine hematopoietic progenitor 32D cl 3 cells were incubated in 1, 10, or 100 μM CBZ 1 h before or immediately after 08 Gy irradiation and assayed for clonogenic survival. Autophagy was assayed by immunoblot for microtubule-associated protein light chain 3 (LC3). In vivo radioprotection and mitigation were determined with C57BL/6NTac mice. Results: CBZ treatment at 1, 10 or 100 μM for 1 h prior to irradiation increased radioresistance (the dose for 37% survival or D0) from control 1.5 ± 0.1 Gy to 2.1 ± 0.2 Gy (P = 0.012), 2.3 ± 0.1 Gy (P = 0.010), and 3.6 ± 0.7 Gy (P = 0.003), respectively; after irradiation increased the extrapolation number () from 1.5 ± 0.3 to 10.1 ± 4.2 (P = 0.011), 5.5 ± 1.7 (P = 0.019), and 3.6 ± 0.8 (P = 0.014), respectively, and increased autophagy. CBZ treated mice 10 min or 24 h before or 10 min or 12 h after 9.25 Gy total body irradiation (TBI) showed increased survival (P = 0.012, 0.011, 0.0002, and 0.017, respectively). Conclusion: CBZ may be a useful radiation protector and mitigator.
KW - Autophagy
KW - Carbamazepine
KW - Radiation mitigation
KW - Radiation protection
UR - http://www.scopus.com/inward/record.url?scp=80053541546&partnerID=8YFLogxK
U2 - 10.3109/09553002.2011.587860
DO - 10.3109/09553002.2011.587860
M3 - Article
C2 - 21728759
AN - SCOPUS:80053541546
SN - 0955-3002
VL - 87
SP - 1052
EP - 1060
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 10
ER -