Histone deacetylase inhibitors protect against and mitigate the lethality of total-body irradiation in mice.
It was hypothesized that histone deacetylase (HDAC) inhibitors may increase survival after total-body irradiation (TBI) based on previous reports demonstrating that HDAC inhibitors stimulate the proliferation of bone marrow stem cells. Using the time for mice to lose 20% or more of their weight as the end point, two HDAC inhibitors, valproic acid and trichostatin-A, were found to reduce lethality in a dose-dependent manner. HDAC inhibitors were effective at reducing lethality when given either 24 h before or 1 h after TBI. The results indicate that HDAC inhibitors have potential for protecting against and mitigating radiation-induced lethality.
Brown
Stephen L
SL
Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202, USA. sbrown1@hfhs.org
Kolozsvary
Andrew
A
Liu
Jianguo
J
Ryu
Samuel
S
Kim
Jae Ho
JH
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology; D014916:Whole-Body Irradiation
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011837:Radiation-Protective Agents; C012589:trichostatin A; D014635:Valproic Acid