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

Abstract

PurposeIonizing 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.MethodsWe 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).ResultsGT3 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.ConclusionsGT3 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.

Radioprotective role of α-tocotrienol against oxidative damage in γ-irradiated human blood cultures

“…It was found that gamma tocotrienol modulates as many as 27 gene clusters in human umbilical vein endothelial cells involved in DNA damage (BERBEE et al, 2012). Pathak et al (2016), suggested several mechanisms to explain how gamma-tocotrienol detoxifies ROS. Gamma-tocotrienol may regulate mitochondrial activity, transcription factors, or endothelial cell surface receptors.…”

“…The vitamin E isoforms tocotrienol are natural dietary antioxidant and a potent radioprotector, with the largest dose reduction factor among all the natural products (GHOSH et al 2009). Many studies do not fully understand how tocotrienol protects against radiation damage but it may regulate apoptotic signals, cytokine production, cholesterol biosynthesis, or progenitor cell mobilization (PATHAK et al, 2016). Moreover, gene-expression profiles suggest that γ-tocotrienol affects a number of genes known to be important for the DNA damage response (BERBEE et al, 2012).…”

Tocopherols and Tocotrienols in Common and Emerging Dietary Sources: Occurrence, Applications, and Health Benefits

“…Furthermore, DNA damage taking place in human white blood cells in vitro appeared to be related to consumption of dietary antioxidants [169]. Additionally, in a recent study [141], human umbilical vein endothelial cells were subjected to gamma-irradiation where gamma-tocotrienol was found to attenuate DNA double-strand breaks. Moreover, the same work showed an increase in the expression of the DNA repair RAD50, therefore highlighting the importance of gamma-tocotrienol and its sources as a potential therapeutic strategy to reduce irradiation-induced genetic diseases.…”

Overview of Radiation-protective Agent Research and Prospects for the Future

“…9) In addition, PATHAK et al have demonstrated that GT3 pretreatment reduced DNA double-strand breaks formation in human umbilical vein endothelial cells (HUVECs), and also decreased chromosomal aberrations in both HUVECs and mouse bone marrow cells after irradiation. 65) Moreover, GT3 increased expression of the DNA-repair gene RAD50 and attenuated radiation-induced RAD50 suppression. Currently, GT3 is being investigated for its ef cacy against 60 Co -irradiation using a NHP model.…”