Ionizing irradiation protection and mitigation of murine cells by carbamazepine is p53 and autophagy independent

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

Research output: Contribution to journalArticle

3 Scopus citations

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. 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.

Original languageEnglish
Pages (from-to)341-354
Number of pages14
JournalIn Vivo
Volume26
Issue number3
StatePublished - May 1 2012
Externally publishedYes

Keywords

  • Autophagy
  • Bone marrow stromal cells
  • Carbamazepine
  • Lewis lung carcinoma cells
  • Murine hematopoietic progenitor cells
  • Radiation mitigation
  • Radioprotection
  • p53

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    Kim, H., Bernard, M. E., Farkas, A., Goff, J., Kalash, R., Houghton, F., Shields, D., Franicola, D., Dixon, T., Zhang, X., Epperly, M., Wang, H., Cobanoglu, M. C., & Greenberger, J. S. (2012). Ionizing irradiation protection and mitigation of murine cells by carbamazepine is p53 and autophagy independent. In Vivo, 26(3), 341-354.