TY - JOUR T1 - Ionizing Irradiation Protection and Mitigation of Murine Cells by Carbamazepine is p53 and Autophagy Independent JF - In Vivo JO - In Vivo SP - 341 LP - 354 VL - 26 IS - 3 AU - HYUN KIM AU - MARK E. BERNARD AU - AMY FARKAS AU - JULIE GOFF AU - RONNY KALASH AU - FRANK HOUGHTON AU - DONNA SHIELDS AU - DARCY FRANICOLA AU - TRACY DIXON AU - XICHEN ZHANG AU - MICHAEL EPPERLY AU - HONG WANG AU - MURAT CAN COBANOGLU AU - JOEL S. GREENBERGER Y1 - 2012/05/01 UR - http://iv.iiarjournals.org/content/26/3/341.abstract N2 - 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. ER -