Original Articles Protection of Cellular DNA and Membrane from g-Radiation–Induced Damages and Enhancement in DNA Repair by Sesamol Gopakumar Gopinathan Nair and Cherupally Krishnan Krishnan Nair Abstract Sesamol (SM), a nutritional phenolic antioxidant compound present in sesame seeds, protected pBR 322 DNA from gamma radiation–induced damages. SM prevented gamma radiation–induced degradation of covalently closed circular form of plasmid DNA in a concentration-dependent manner. Also SM protected cellular DNA of mouse blood leukocytes exposed to 4 Gy gamma radiation, ex vivo, as revealed by the data from alkaline comet assay studies. SM (5 mM) showed a faster time-dependant decrease of the radiation-induced DNA damage in mouse blood leukocytes following postirradiation incubation ex vivo, which could be attributed to enhanced DNA repair. SM protected the biomembranes from radiation-induced lipid peroxidation. Thus, SM could act as a radioprotector for the biomembranes and cellular DNA against the deleterious effects of ionizing radiation. Key words: radioprotector, sesamol (3,4-methylenedioxyphenol), pBR 322, DNA damage, DNA repair, comet assay Introduction I onizing radiation inflicts deleterious effects to living or- ganisms through the generation of reactive oxygen species, which damages vital cellular targets such as DNA and membrane. 1 The DNA damages include strand breaks, base damage, sugar damage, and crosslinks of inter- and in- trastrand types. 2,3 Many natural and synthetic compounds have been found to have considerable radioprotective ability. 4 The radioprotectors can elicit their action by various mecha- nisms such as inhibiting the formation of reactive free radi- cals, detoxification of radiation induced species, target stabilization, and enhancing the repair and recovery process. 5 Sesame (Sesamum indicum) is an important oilseed crop with nutritional and medicinal values and its seeds contain lignan compounds—sesamin and sesamolin. Sesamol (SM) (Fig. 1), a phenolic antioxidant compound, is a derivative of sesamolin and is generated on roasting sesame seeds. 6–9 It exhibits various beneficial biological effects 10 such as che- mopreventive, antimutagenic, and antihepatotoxic activi- ties 11–13 and induction of growth arrest and apoptosis in cancer and cardiovascular cells. 14 The radioprotective effects of SM on gamma radiation–induced DNA damage and lipid peroxidation have been reported in cultured human lym- phocytes. SM pretreatment decreased radiation-induced micronuclei, chromosomal aberration, and oxidative stress in human lymphocytes exposed to gamma radiation ex vivo. 15 SM was reported to have radioprotective action in doses above 25 mg/kg body weight (bw) in mice. Pretreatment of mice with SM (50 mg/kg bw) before exposure to 15 Gy gamma radiation significantly reduced dead, inflammatory, mitotic, and goblet cells in irradiated jejunum and also in- creased crypt cells, thus protecting the gastrointestinal sys- tem from radiation-induced damages. 16 In the present study, SM was evaluated for its efficiency as a radioprotective agent against gamma radiation–induced cellular DNA and mem- brane damage and also its effect on cellular DNA repair under ex vivo conditions. Materials and Methods Chemicals SM (3,4-methylenedioxyphenol) was obtained from Spectrochem. Na 2 -ethylene diamine tetra-acetic acid and Department of Radiation Biology, Amala Cancer Research Centre, Thrissur, Kerala, India. Address correspondence to: Cherupally Krishnan Krishnan Nair; Department of Radiation Biology, Amala Cancer Research Centre; Amala Nagar, Thrissur 680 555, Kerala, India E-mail: ckknair@yahoo.com CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Volume 25, Number 6, 2010 ª Mary Ann Liebert, Inc. DOI: 10.1089/cbr.2010.0803 629