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

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

Author information

1
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.
2
Department of Engineering and Engineering Physics, Southern Arkansas University, Magnolia, Arkansas, USA.
3
Armed Forces Radiobiology Research Institute, USUHS, Bethesda, Maryland, USA.
4
Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
5
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.
6
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
7
Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.

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

PMID:
27216753
PMCID:
PMC4967083
DOI:
10.1007/s11095-016-1950-0
[Indexed for MEDLINE]
Free PMC Article

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