title: Ionizing irradiation protection and mitigation of murine cells by carbamazepine is p53 and autophagy independent.
abstract: BACKGROUND
  Carbamazepine, a sodium channel blocker and pro-autophagy agent used in the treatment of epilepsy and trigeminal neuralgia, is also an ionizing radiation mitigator and protector.
  
  
  METHODS
  We measured the effect of carbamazepine, compared to other pro-autophagy drugs (i.e. lithium and valproic acid), on irradiation of autophagy incompetent (Atg5(-/-)) and competent (Atg5(+/+)) mouse embryonic fibroblasts, p53(-/-) and p53(+/+) bone marrow stromal cells, and human IB3, KM101, HeLa, and umbilical cord blood cell and in total body-irradiated or orthotopic tumor-bearing mice.
  
  
  RESULTS
  Carbamazepine, but not other pro-autophagy drugs, was a radiation protector and mitigator for mouse cell lines, independent of apoptosis, autophagy, p53, antioxidant store depletion, and class I phosphatidylinositol 3-kinase, but was ineffective with human cells. Carbamazepine was effective when delivered 24 hours before or 12 hours after total body irradiation of C57BL/6HNsd mice and did not protect orthotopic Lewis lung tumors.
  
  
  CONCLUSIONS
  Carbamazepine is a murine radiation protector and mitigator.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, USA.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bernard
authors.forename: Amy
authors.initials: A
authors.lastname: Farkas
authors.forename: Julie
authors.initials: J
authors.lastname: Goff
authors.forename: Ronny
authors.initials: R
authors.lastname: Kalash
authors.forename: Frank
authors.initials: F
authors.lastname: Houghton
authors.forename: Donna
authors.initials: D
authors.lastname: Shields
authors.forename: Darcy
authors.initials: D
authors.lastname: Franicola
authors.forename: Tracy
authors.initials: T
authors.lastname: Dixon
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Epperly
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Murat Can
authors.initials: MC
authors.lastname: Cobanoglu
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001343:Autophagy / Q000187:drug effects* / Q000528:radiation effects; D000071187:Autophagy-Related Protein 5; D002220:Carbamazepine / Q000494:pharmacology* / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D055786:Gene Knockout Techniques; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D018021:Lithium Chloride / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology; D014916:Whole-Body Irradiation
chemical_list: D000975:Antioxidants; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D002220:Carbamazepine; D014635:Valproic Acid; D058534:Class I Phosphatidylinositol 3-Kinases; D018021:Lithium Chloride