Fardid Reza, Salajegheh Ashkan, Mosleh-Shirazi Mohammad Amin, Sharifzadeh Sedigheh, Okhovat Mohammad Ali, Najafi Masoud, Rezaeyan Abolhasan, Abaszadeh Akbar
Department of Radiology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Ionizing and Non-ionizing Radiation Protection Research Center, Department of Radiotherapy and Oncology, Shiraz University of Medical Sciences, Shiraz, Iran.
Cell J. 2017 Jul-Sep;19(2):324-331. doi: 10.22074/cellj.2016.3857. Epub 2017 Feb 22.
In this study, we evaluated the bystander effect of radiation on the regulation of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and 8-hydroxydeoxyguanosine (8-OHdG) in lung tissues of Sprague-Dawley rats with and without pre-administration of melatonin. A 2×2 cm area of the pelvis of male Sprague-Dawley rats with and without pre-administration of melatonin (100 mg/kg) by oral and intraperitoneal injection was irradiated with a 3 Gy dose of 1.25 MeV γ-rays. Alterations in the levels of COX-2, iNOS, and 8-OHdG in the out-of-field lung areas of the animals were detected by enzyme immunoassay. The bystander effect significantly increased COX-2, iNOS, and 8-OHdG levels in non-targeted lung tissues (P<0.05). Melatonin ameliorated the bystander effect of radiation and significantly reduced the level of all examined biomarkers (P<0.05). The results indicated that the ameliorating effect of a pre-intraperitoneal (IP) injection of melatonin was noticeably greater compared to oral pre-administration. Our findings revealed that the bystander effect of radiation could induce oxidative DNA damage and increase the levels of imperative COX-2 and iNOS in non-targeted lung tissues. Interestingly, melatonin could modulate the indirect destructive effect of radiation and reduce DNA damage in non-targeted cells.
在本研究中，我们评估了辐射对褪黑素预处理和未预处理的Sprague-Dawley大鼠肺组织中环氧合酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）和8-羟基脱氧鸟苷（8-OHdG）调节的旁观者效应。对口服和腹腔注射褪黑素（100mg/kg）以及未进行预处理的雄性Sprague-Dawley大鼠骨盆处2×2cm区域给予3Gy剂量的1.25MeVγ射线照射。通过酶免疫测定法检测动物非照射肺区域中COX-2、iNOS和8-OHdG水平的变化。旁观者效应显著增加了非靶向肺组织中COX-2、iNOS和8-OHdG的水平（P<0.05）。褪黑素减轻了辐射的旁观者效应，并显著降低了所有检测生物标志物的水平（P<0.05）。结果表明，与口服预处理相比，腹腔内（IP）注射褪黑素的改善效果明显更大。我们的研究结果表明，辐射的旁观者效应可诱导氧化性DNA损伤，并增加非靶向肺组织中关键的COX-2和iNOS水平。有趣的是，褪黑素可以调节辐射的间接破坏作用，并减少非靶向细胞中的DNA损伤。
