Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello 0310 Oslo, Norway.
Radiat Res. 2012 Jan;177(1):35-43. doi: 10.1667/rr2694.1. Epub 2011 Oct 28.
Radiation-induced bystander effects have been studied extensively due to their potential implications for cancer therapy and radiation protection; however, a complete understanding of the molecular mechanisms remains to be elucidated. In this study, we monitored transcriptional responses to γ radiation in irradiated and bystander fibroblasts simultaneously employing a genome-wide microarray approach to determine factors that may be modulated in the generation or propagation of the bystander effect. For the microarray data we employed analysis at both the single-gene and gene-set level to place the findings in a biological context. Unirradiated bystander fibroblasts that were recipients of growth medium harvested from irradiated cultures 2 h after exposure to 2 Gy displayed transient enrichment in gene sets belonging to ribosome, oxidative phosphorylation and neurodegenerative disease pathways associated with mitochondrial dysfunctions. The response to direct irradiation was characterized by induction of signaling and apoptosis genes and the gradual formation of a cellular immune response. A set of 14 genes, many of which were regulated by p53, were found to be induced early after irradiation (prior to medium transfer) and may be important in the generation or propagation of the bystander effect.
由于辐射诱发的旁观者效应可能对癌症治疗和辐射防护具有潜在影响，因此人们对此进行了广泛的研究；然而，对于其分子机制仍有待阐明。在这项研究中，我们采用全基因组微阵列方法同时监测照射和旁观者成纤维细胞对γ辐射的转录反应，以确定可能在旁观者效应的产生或传播中被调节的因素。对于微阵列数据，我们采用了单个基因和基因集水平的分析，以便将这些发现置于生物学背景下。在受到 2 Gy 照射 2 小时后，未受照射的旁观者成纤维细胞接收来自照射培养物的生长培养基，其核糖体、氧化磷酸化和与线粒体功能障碍相关的神经退行性疾病途径的基因集短暂富集。直接照射的反应特征是信号和细胞凋亡基因的诱导以及细胞免疫反应的逐渐形成。一组 14 个基因，其中许多受 p53 调节，在照射后早期（在培养基转移之前）被诱导，可能在旁观者效应的产生或传播中很重要。
