Partial volume rat lung irradiation: Temporal fluctuations of in-field and out-of-field DNA damage and inflammatory cytokines following irradiation
Partial volume rat lung irradiation: Temporal fluctuations of in-field and out-of-field DNA damage and inflammatory cytokines following irradiation
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DOI：
10.1080/09553000600568002
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发表时间：
2005-12-01
影响因子：
2.6
通讯作者：
Hill, RP
中科院分区：
文献类型：
--
作者：
Calveley, VL;Khan, MA;Hill, RP
目的：本研究探讨了部分体积照射后肺不同区域炎症细胞因子和巨噬细胞的早期激活。我们研究了DNA损伤，细胞因子的表达和巨噬细胞活化在16周postradiation.Materials和方法的时间波动：我们照射了10戈伊的Sprague-Dawley大鼠下肺。微核试验用于检测DNA损伤。使用实时逆转录-聚合酶链反应（RT-PCR）分析白细胞介素-1 α（IL-1 α）、白细胞介素-1 β（IL-1 β）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF-α）和转化生长因子β（TGF-β）相对于甘油醛-3-磷酸脱氢酶（GAPDH）的RNA表达。结果：DNA损伤的表达、巨噬细胞的活化及炎性细胞因子的表达均呈周期性波动。细胞因子表达的初始诱导和巨噬细胞的活化发生在照射后的非常早的时间（1小时）。在照射后的较晚时间（长达16周）也观察到细胞因子表达和巨噬细胞活化的波。DNA损伤也发生在一个循环模式，虽然这是不太明显的场外。细胞因子和活化的巨噬细胞的水平升高到一个类似的程度都在和外地，而有一个更大的微核产量在外地比out-of-field.Conclusions：部分体积照射引发的炎症反应发生在整个大鼠肺在非常早期的时间照射后，并保持在一个循环模式，到后来的时候，预计功能症状的发作。我们推测，活性氧（ROS）诱导的这种反应发挥了重要的作用，在现场和场外的DNA损伤的诱导。
Purpose: The current study investigated the early activation of inflammatory cytokines and macrophages in different regions of the lung following partial volume irradiation. We examined temporal fluctuations in DNA damage, cytokine expression and macrophage activation during 16 weeks post-irradiation.Materials and methods: We irradiated the lower lung of Sprague-Dawley rats with 10 Gy. A micronucleus assay was used to examine DNA damage. Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to analyse the RNA expression of Interleukin-1 alpha (IL-1 alpha), Interleukin-1 beta (IL-1 beta), Interleukin-6 (IL-6), Tumour Necrosis Factor alpha (TNF-alpha) and Transforming Growth Factor beta (TGF-beta) relative to Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH). The activation of macrophages was determined using the antibody ED-1 for immunohistochemical analysis.Results: The expression of DNA damage, the activation of macrophages and the expression of inflammatory cytokines all fluctuated in a cyclic pattern. The initial induction of cytokine expression and the activation of macrophages occurred at very early times ( 1 h) following irradiation. Waves of cytokine expression and macrophage activation were also seen at later times ( up to 16 weeks) following irradiation. DNA damage also occurred in a cyclic pattern though this was less pronounced out-of-field. The levels of cytokines and activated macrophages were elevated to a similar degree both in-and out-of-field, whereas there was a greater micronuclei yield in-field than out-of-field.Conclusions: An inflammatory response triggered by the partial volume irradiation occurs in the whole rat lung at very early times following irradiation and is maintained in a cyclic pattern to later times when the onset of functional symptoms is expected. We hypothesize that Reactive Oxygen Species (ROS) induced by this response play an important role in the induction of both in-field and out-of-field DNA damage.