Radiation and Environmental Biophysics

, 50:585

Radioprotection by the histone deacetylase inhibitor phenylbutyrate

Authors

    • Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI)Uniformed Services University
  • Stuart Cohen
    • Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI)Uniformed Services University
  • Michael Stewart
    • Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI)Uniformed Services University
  • Rafael Rivas
    • Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI)Uniformed Services University
  • Paul Lison
    • Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI)Uniformed Services University
    • Department of Occupational and Environmental MedicineUniversity of Paris
Original Paper

DOI: 10.1007/s00411-011-0384-7

Cite this article as:
Miller, A.C., Cohen, S., Stewart, M. et al. Radiat Environ Biophys (2011) 50: 585. doi:10.1007/s00411-011-0384-7

Abstract

The histone deacetylase inhibitor (HDAC), phenylbutyrate (PB), is a novel anti-tumor agent. Studies have demonstrated that HDAC inhibitors can suppress cutaneous radiation syndrome and stimulate hematopoiesis. The objective of this study was to test the ability of PB treatment to protect against acute gamma-radiation-induced lethality in the DBA/2 mouse model. A 30-day radiation lethality study was used to assess radioprotective capability of PB. Mechanisms were evaluated using western blots, flow cytometry, and the single-cell gel electrophoresis assay. Western blot studies showed that PB treatment acetylated histones in vivo. For radiation protection studies, prophylactic administration of PB (24 h preradiation; 1–50 mg/kg) provided radioprotection against gamma radiation (8–9.5 Gy) and PB demonstrated a DRF of 1.31 (P = 0.001; 95% confidence interval: 1.27, 1.36). When PB (10 mg/kg) was administered post-radiation (4 h), it also provided significant radioprotection at 8.0 Gy radiation (P = 0.022). PB treatment before radiation was associated with significant elevations in neutrophils and platelets following radiation. Results from single-cell gel electrophoresis of peripheral blood leukocytes demonstrated that PB treatment before radiation can attenuate DNA damage and inhibit radiation-induced apoptosis. These results indicate that an HDAC inhibitor like PB has potential as a radiation protector and that mechanisms of action include attenuation of DNA damage and inhibition of apoptosis.

Abbreviations

PB

Phenylbutyrate

HDAC

Histone deacetylase inhibitor

Copyright information

© Springer-Verlag (outside the USA) 2011