Spatial function of the oxidative DNA damage response in radiation induced bystander effects in intra- and inter-system of Caenorhabditis elegans.

Spatial function of the oxidative DNA damage response in radiation induced bystander effects in intra- and inter-system of Caenorhabditis elegans.
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秀丽隐杆线虫系统内和系统间辐射诱导旁观者效应中氧化DNA损伤反应的空间功能

DOI:
10.18632/oncotarget.17229
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发表时间:
2017-08-01
期刊:
影响因子:
--
通讯作者:
Wu L
Wu L
中科院分区:
其他
文献类型:
--
作者:
Li Q;Shi J;Chen L;Zhan F;Yuan H;Wang J;Xu A;Wu L

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虽然辐射诱导的旁观者效应(里贝)中的信号转导已在体内外得到研究,但这些信号转导的空间功能,尤其是相关的信号转导通路,还没有完全阐明。在目前的研究中,在C.结果表明,照射后咽内系统和外阴间系统均对线虫生殖系有明显的损伤作用,其中外阴照射对线虫生殖系的损伤更严重,甚至对F1代线虫也有损伤作用。空间功能分析表明,mrt-2/hus-1/cep-1/ced-4的DDR关键组分在生殖细胞中是两个部位照射所必需的,而体细胞中的这些组分不是(cep-1/ced-4)或部分(mrt-2/hus-1)促进凋亡所必需的。此外,生产的活性氧(ROS)表示的超氧化物歧化酶的表达和未折叠的蛋白质反应的线粒体被发现全身参与启动这些过程的两个站点照射。这些结果将使我们更好地了解里贝在体内的作用机制,并对评估放射治疗的临床意义具有重要价值。
Though the signaling events involved in radiation induced bystander effects (RIBE) have been investigated both in vitro and in vivo, the spatial function of these communications, especially the related signaling pathways, is not fully elucidated. In the current study, significant increases of DNA damage were clearly observed in C. elegans germline upon irradiation to both intra-system of posterior pharynx and inter-system of vulva, in which more severe damage, even to F1 generation worms, was shown for vulva irradiation. Spatial function assay indicated the DDR key components of mrt-2/hus-1/cep-1/ced-4 were indispensable in germ cells for both sites irradiation, while those components in somatic cells were either not (cep-1/ced-4) or partially (mrt-2/hus-1) required to promote apoptosis. Moreover, production of reactive oxygen species (ROS) indicated by the superoxide dismutase expression and the unfolded protein response of the mitochondria was found systemically involved in the initiation of these processes for both two site irradiation. These results will give a better understanding of the RIBE mechanisms in vivo, and invaluable to assess the clinical relevance to radiotherapy.
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