Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Pharm Res. 2016 May 23. Epub 2016 May 23. PMID: 27216753

Abstract Author(s):

Rupak Pathak, Abdel Bachri, Sanchita P Ghosh, Igor Koturbash, Marjan Boerma, Regina K Binz, Jeffrey R Sawyer, Martin Hauer-Jensen

Article Affiliation:

Rupak Pathak

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 isoformγ-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 ofγ-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.

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