Partial volume rat lung irradiation; assessment of early DNA damage in different lung regions and effect of radical scavengers
Partial volume rat lung irradiation; assessment of early DNA damage in different lung regions and effect of radical scavengers
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DOI：
10.1016/s0167-8140(02)00325-0
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发表时间：
2003-01-01
影响因子：
5.7
通讯作者：
Hill, RP
中科院分区：
文献类型：
--
作者：
Khan, MA;Van Dyk, J;Hill, RP
目的：这些研究的目的是研究辐射诱导的大鼠肺中的场内和场外DNA损伤作为剂量和各种照射体积的函数。他们还确定是否超氧化物歧化酶（SOD）和硝基-L-精氨酸甲酯（L-NAME）保护这种damage.Methods和材料：整个肺，或不同体积的下或上肺的Sprague-Dawley大鼠暴露剂量高达20戈伊的Co-60 γ射线。辐射诱导的DNA损伤定量成纤维细胞中获得的18它照射后，从照射和屏蔽肺区域使用微核试验。SOD（CuZnSOD：10 mg/kg体重; MnSOD：50-100 mg/kg体重）和L-NAME（0.2 mg/kg体重）的辐射防护作用。结果：在15戈伊剂量范围内，微核形成与剂量呈近似线性关系。当70%的肺体积接受10戈伊照射时，照射下肺产生的微核（MN）/双核细胞（BN）数与全肺照射后所观察到的相似（0.91 MN/ BN），而照射上肺仅产生0.66 MN/BN。下肺照射后，屏蔽的上肺（肺体积的30%）显示出实质性（场外）损伤（0.43 MN/BN）。当30%的肺被给予10戈伊时，被照射的上肺或下肺显示出相似量的场内损伤（0.43 MN/BN），但这小于在照射70%的肺体积后所看到的损伤。对于30%的下肺照射，屏蔽的上肺仅显示出小的场外效应（0.1 MN/BN）。对于两种照射量，在上肺照射后，屏蔽下肺中的效应相似或较小。在10戈伊照射前注射SOD或10 Gy照射后注射L-NAME，均能减少野内外的DNA损伤，但野外损伤的百分比（50-60%）远大于野内损伤（10-30%）。在全肺照射（10戈伊）后，在来自左肺的成纤维细胞中观察到比来自右肺的成纤维细胞显著更大的DNA损伤（0.93 MN/BN对0.82 MN/BN）。全肺照射后，在成纤维细胞中观察到的DNA损伤，从下肺和上lung.Conclusions：部分肺照射下肺维持更多的照射后比上肺的DNA损伤，而外地的影响主要是在上肺（即下肺照射）。全肺照射后，左肺比右肺受到更大的损伤，但上下肺之间没有差异。SOD和L-NAME的保护作用表明，由辐射诱导的炎性细胞因子可能参与引发反应，导致产生反应性氧自由基和一氧化氮，从而引起辐射场内外的间接DNA损伤。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Purpose: These studies were designed to examine radiation-induced in-field and out-of-field DNA damage in rat lung as a function of dose and various volumes of irradiation. They also determined whether superoxide dismutase (SOD) and nitro-L-arginine methyl ester (L-NAME) protected against this damage.Methods and materials: The whole lung, or various volumes of the lower or upper lungs of Sprague-Dawley rats were exposed to doses up to 20 Gy of Co-60 gamma rays. Radiation-induced DNA damage was quantified in fibroblasts obtained at 18 It after irradiation from both irradiated and shielded lung regions using a micronucleus assay. The radioprotective role of SOD (CuZnSOD: 10 mg/kg body weight; MnSOD: 50-100 mg/kg body weight) and L-NAME (0.2 mg/kg body weight.) in vivo was determined by injecting them into rats 30 min before or immediately after a dose of 10 Gy.Results: Micronucleus formation was approximately linear with dose up to 15 Gy. When 70% of the lung volume was irradiated with 10 Gy, irradiated lower lung gave similar numbers of micronuclei (MN)/binucleate cell (BN) to that observed following whole lung irradiation (0.91 MN/ BN), whereas the irradiated upper lung gave only 0.66 MN/BN. Following lower lung irradiation, the shielded upper lung (30% of lung volume) showed substantial (out-of-field) damage (0.43 MN/BN). When 30% of the lung was given 10 Gy, irradiated upper or lower lung showed similar amounts of in-field damage (0.43 MN/BN) but this was smaller than that seen following irradiation of 70% of the lung volume. For 30% lower lung irradiation, the shielded upper lung showed only a small out-of-field effect (0.1 MN/BN). For both volumes of irradiation there was a similar or smaller effect in the shielded lower lung after upper lung irradiation. Injection of SOD before or L-NAME after 10 Gy to the lower 70% lung volume resulted in a reduction in DNA damage both in-field and out-of-field but the percentage was much greater for out-of-field damage (50-60%) than for in-field damage (10-30%). Following whole lung irradiation (10 Gy) significantly greater DNA damage was observed in fibroblasts from the left lung than from the right lung (0.93 MN/BN vs. 0.82 MN/BN). Following whole lung irradiation there was no significant difference in DNA damage observed in fibroblasts from the lower lung and the upper lung.Conclusions: With partial lung irradiation the lower lung sustains more in-field DNA damage following irradiation than the upper lung, whereas out-of-field effects are observed primarily in the upper lung (i.e. following lower lung irradiation). Following whole lung irradiation the left lung sustains more damage than the right lung but there is no difference between the upper and lower lung. The protective effects of SOD and L-NAME suggest that inflammatory cytokines induced by the irradiation may be involved in the initiation of a reaction resulting in the production of reactive oxyradicals and nitric oxide that cause indirect DNA damage both in and out of the radiation field. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.