The autophagy-inducing drug carbamazepine is a radiation protector and mitigator

Int J Radiat Biol. 2011 Oct;87(10):1052-60. doi: 10.3109/09553002.2011.587860. Epub 2011 Jul 5.

Abstract

Purpose: To determine whether Carbamazepine (CBZ) is a radiation protector and/or mitigator.

Materials and 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).

Conclusion: CBZ may be a useful radiation protector and mitigator.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Autophagy / radiation effects*
  • Carbamazepine / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / radiation effects*
  • Radiation Injuries / metabolism
  • Radiation Injuries / pathology
  • Radiation Injuries / prevention & control
  • Radiation Protection / methods
  • Radiation-Protective Agents / pharmacology*
  • Time Factors
  • Whole-Body Irradiation

Substances

  • Microtubule-Associated Proteins
  • Radiation-Protective Agents
  • Carbamazepine