title: The autophagy-inducing drug carbamazepine is a radiation protector and mitigator.
abstract: OBJECTIVE
  To determine whether Carbamazepine (CBZ) is a radiation protector and/or mitigator.
  
  
  METHODS
  Murine hematopoietic progenitor 32D cl 3 cells were incubated in 1, 10, or 100 μM CBZ 1 h before or immediately after 0-8 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 D(0)) 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 (ñ) 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).
  
  
  CONCLUSIONS
  CBZ may be a useful radiation protector and mitigator.
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
authors: Hyun
authors: H
authors: Kim
authors: Mark E
authors: ME
authors: Bernard
authors: John
authors: J
authors: Flickinger
authors: Michael W
authors: MW
authors: Epperly
authors: Hong
authors: H
authors: Wang
authors: Tracy M
authors: TM
authors: Dixon
authors: Donna
authors: D
authors: Shields
authors: Frank
authors: F
authors: Houghton
authors: Xichen
authors: X
authors: Zhang
authors: Joel S
authors: JS
authors: Greenberger
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000528:radiation effects*; D002220:Carbamazepine / Q000494:pharmacology*; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000528:radiation effects*; D011832:Radiation Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011835:Radiation Protection / Q000379:methods; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors; D014916:Whole-Body Irradiation
chemical_list: D008869:Microtubule-Associated Proteins; D011837:Radiation-Protective Agents; D002220:Carbamazepine