Expression Levels of Two DNA Repairrelated Genes under 8 Gy Ionizing Radiation and 100 Mg/Kg Melatonin Delivery In Rat Peripheral Blood

Abstract

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 highdose 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 Xrcc4 and Xrcc6 (Ku70) in order to examine the effect of melatonin on repair of DNA double-strand breaks (BSBs) caused by 8Gy ionizing radiation. Methods: One hundred eight male Wistar rats were irradiated with a whole body gamma radiation dose of 8Gy with or without melatonin pretreatments. They were divided into six different groups of control, 100 mg/kg melatonin alone, 8Gy irradiation alone, vehicle alone, vehicle plus 8Gy irradiation and 100 mg/kg melatonin plus 8Gy irradiation. Peripheral blood samples were collected at 8, 24 and 48 h after irradiation. Ku70 and Xrcc4 gene expression were evaluated by real-time quantitative polymerase chain reaction (qPCR) technique and analyzed by one-way ANOVA test. Results: Expression of Ku70 and Xrcc4 genes normalized against Hprt gene showed significant difference in melatonin plus irradiation group at 8h compared to the control group (p<0.05). At 24h post irradiation, gene expression changes were significantly upregulated in irradiation-alone group as well as melatonin plus irradiation group (p<0.05). No significant change was found in any groups compared to control group at 48 h time point. Conclusion: We concluded that, by increasing expression level of Ku70 and Xrcc4 genes, 100 mg/kg melatonin administration 8 and 24 h before 8 Gyionizing radiation can significantly affect the repair of DNA DSBs in NHEJ pathway.

Keywords

• Ionizing Radiation
• Melatonin
• Gene Expression Level
• Ku70
• Xrcc4