Gamma-Tocotrienol Pretreatment Reduces DNA Damage in Lymphocytes of Normal Subjects and Patients with Down's Syndrome

Abstract The degeneration process associated with Down syndrome (DS) has been partly attributed to the excess hydrogen peroxide formation as a result of excess expression of SOD gene. The increased production of hydroxyl radicals result in damage to macromolecules including the DNA. In this study we evaluated the effect of gamma-tocotrienol (GTT), a subfamily of vitamin E, on DNA damage as measured by the single gel electrophoresis (otherwise known as the comet assay) in lymphocytes of normal and DS subjects. We also studied whether gamma-tocotrienol can reduce DNA damage when the DNA repair phase of the cell cycle is inhibited with caffeine. Blood samples were taken from 11 normal and 8 DS children aged 1-7 years old. The lymphocytes were harvested and then cultured in RPMI folate free medium for 72 h before treatment with 20 uM GTT or 5 mM caffeine. For the study on gamma-tocotrienol pretreatment on caffeine treated cells, the lymphocytes were incubated with GTT for 2 h before the addition of caffeine into the culture medium. Results showed that GTT significantly reduced basal DNA damage as well as when DNA repair was inhibited in lymphocytes taken from DS and normal subjects suggesting a potential role of GTT in the treatment and management of DS patients