Expression Levels of Two DNA Repair-related Genes under ۸ Gy Ionizing Radiation and ۱۰۰ Mg/Kg Melatonin Delivery In Rat Peripheral Blood

Background: After radiation therapy (RT), some health hazards including DNA damages may occur where melatonin can play a protective role due to free radical generation. On the other hand, serious accidental overexposures may occur during RT due to nuclear accidents which necessitate the need for study on exposure to high-dose radiations during treatments.Objective: The aim of this study was to study the expression level of two genes in non-homologous end joining (NHEJ) pathways named Xrcc۴ and Xrcc۶ (Ku۷۰) in order to examine the effect of melatonin on repair of DNA double-strand breaks (BSBs) caused by ۸Gy ionizing radiation.Methods: One hundred eight male Wistar rats were irradiated with a whole body gamma radiation dose of ۸Gy with or without melatonin pretreatments. They were divided into six different groups of control, ۱۰۰ mg/kg melatonin alone, ۸Gy irradiation alone, vehicle alone, vehicle plus ۸Gy irradiation and ۱۰۰ mg/kg melatonin plus ۸Gy irradiation. Peripheral blood samples were collected at ۸, ۲۴ and ۴۸ h after irradiation. Ku۷۰ and Xrcc۴ gene expression were evaluated by real-time quantitative polymerase chain reaction (qPCR) technique and analyzed by one-way ANOVA test.Results: Expression of Ku۷۰ and Xrcc۴ genes normalized against Hprt gene showed significant difference in melatonin plus irradiation group at ۸h compared to the control group (p<۰.۰۵). At ۲۴h post irradiation, gene expression changes were significantly upregulated in irradiation-alone group as well as melatonin plus irradiation group (p<۰.۰۵). No significant change was found in any groups compared to control group at ۴۸ h time point.Conclusion: We concluded that, by increasing expression level of Ku۷۰ and Xrcc۴ genes, ۱۰۰ mg/kg melatonin administration ۸ and ۲۴ h before ۸ Gyionizing radiation can significantly affect the repair of DNA DSBs in NHEJ pathway.

Keywords:

Ionizing radiation , Melatonin , Gene Expression Level , Ku۷۰ , Xrcc۴