title: The Vitamin E Analog Gamma-Tocotrienol (GT3) Suppresses Radiation-Induced Cytogenetic Damage.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed I, Suite 238, 4301 West Markham, Slot 522-3, Little Rock, Arkansas, 72205, USA. rpathak@uams.edu.
authors.forename: Rupak
authors.initials: R
authors.lastname: Pathak
authors.affiliation: Department of Engineering and Engineering Physics, Southern Arkansas University, Magnolia, Arkansas, USA.
authors.forename: Abdel
authors.initials: A
authors.lastname: Bachri
authors.affiliation: Armed Forces Radiobiology Research Institute, USUHS, Bethesda, Maryland, USA.
authors.forename: Sanchita P
authors.initials: SP
authors.lastname: Ghosh
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed I, Suite 238, 4301 West Markham, Slot 522-3, Little Rock, Arkansas, 72205, USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Regina K
authors.initials: RK
authors.lastname: Binz
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Sawyer
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed I, Suite 238, 4301 West Markham, Slot 522-3, Little Rock, Arkansas, 72205, USA.|Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011832:Radiation Injuries / Q000188:drug therapy*; D011839:Radiation, Ionizing; D024508:Tocotrienols / Q000008:administration & dosage*; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D024508:Tocotrienols; D014810:Vitamin E; D045643:DNA Repair Enzymes
keywords: DNA repair; chromosomal aberrations; endothelial cells; gamma-tocotrienol; ionizing radiation