The Vitamin E Analog Gamma-Tocotrienol (GT3) Suppresses Radiation-Induced Cytogenetic Damage

Pharm Res. 2016 Sep;33(9):2117-25. doi: 10.1007/s11095-016-1950-0. Epub 2016 May 23.

Abstract

Purpose: Ionizing radiation (IR) generates reactive oxygen species (ROS), which cause DNA double-strand breaks (DSBs) that are responsible for cytogenetic alterations. Because antioxidants are potent ROS scavengers, we determined whether the vitamin E isoform γ-tocotrienol (GT3), a radio-protective multifunctional dietary antioxidant, can suppress IR-induced cytogenetic damage.

Methods: We measured DSB formation in irradiated primary human umbilical vein endothelial cells (HUVECs) by quantifying the formation of γ-H2AX foci. Chromosomal aberrations (CAs) were analyzed in irradiated HUVECs and in the bone marrow cells of irradiated mice by conventional and fluorescence-based chromosome painting techniques. Gene expression was measured in HUVECs with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

Results: GT3 pretreatment reduced DSB formation in HUVECS, and also decreased CAs in HUVECs and mouse bone marrow cells after irradiation. Moreover, GT3 increased expression of the DNA-repair gene RAD50 and attenuated radiation-induced RAD50 suppression.

Conclusions: GT3 attenuates radiation-induced cytogenetic damage, possibly by affecting RAD50 expression. GT3 should be explored as a therapeutic to reduce the risk of developing genetic diseases after radiation exposure.

Keywords: DNA repair; chromosomal aberrations; endothelial cells; gamma-tocotrienol; ionizing radiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Bone Marrow Cells / drug effects
  • Cells, Cultured
  • Chromosome Aberrations / drug effects*
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Repair / drug effects
  • DNA Repair Enzymes / genetics
  • Female
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Radiation Injuries / drug therapy*
  • Radiation, Ionizing
  • Tocotrienols / administration & dosage*
  • Vitamin E / administration & dosage*

Substances

  • Antioxidants
  • Tocotrienols
  • Vitamin E
  • DNA Repair Enzymes