Document Detail


Ionizing irradiation protection and mitigation of murine cells by carbamazepine is p53 and autophagy independent.
MedLine Citation:
PMID:  22523285     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
MATERIALS AND 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.
CONCLUSION: Carbamazepine is a murine radiation protector and mitigator.
Authors:
Hyun Kim; Mark E Bernard; Amy Farkas; Julie Goff; Ronny Kalash; Frank Houghton; Donna Shields; Darcy Franicola; Tracy Dixon; Xichen Zhang; Michael Epperly; Hong Wang; Murat Can Cobanoglu; Joel S Greenberger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  In vivo (Athens, Greece)     Volume:  26     ISSN:  1791-7549     ISO Abbreviation:  In Vivo     Publication Date:    2012 May-Jun
Date Detail:
Created Date:  2012-04-23     Completed Date:  2012-08-13     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8806809     Medline TA:  In Vivo     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  341-54     Citation Subset:  IM    
Affiliation:
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / metabolism
Apoptosis / drug effects,  radiation effects
Autophagy / drug effects*,  radiation effects
Carbamazepine / pharmacology*,  therapeutic use
Carcinoma, Lewis Lung / drug therapy,  pathology,  radiotherapy
Cell Line, Tumor
Cell Survival / drug effects,  radiation effects
Cells, Cultured
Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism
Female
Fetal Blood / cytology
Fibroblasts / drug effects,  metabolism,  radiation effects
Gene Knockout Techniques
Hematopoietic Stem Cells / drug effects,  radiation effects
Lithium Chloride / pharmacology
Membrane Potential, Mitochondrial / drug effects
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins / genetics,  metabolism
Neoplasm Transplantation
Radiation, Ionizing
Radiation-Protective Agents / pharmacology*,  therapeutic use
Transplantation, Heterologous
Tumor Burden / drug effects,  radiation effects
Tumor Suppressor Protein p53 / metabolism*
Valproic Acid / pharmacology
Whole-Body Irradiation
Grant Support
ID/Acronym/Agency:
T32 AG021885-10/AG/NIA NIH HHS; T32AG21885/AG/NIA NIH HHS; U19 AI068021-08/AI/NIAID NIH HHS; U19A1068021//PHS HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Atg5 protein, mouse; 0/Microtubule-Associated Proteins; 0/Radiation-Protective Agents; 0/Tumor Suppressor Protein p53; 298-46-4/Carbamazepine; 7447-41-8/Lithium Chloride; 99-66-1/Valproic Acid; EC 2.7.1.137/Class I Phosphatidylinositol 3-Kinases
Comments/Corrections

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