Differential gene expression in human fibroblasts after alpha-particle emitter 211At compared with 60Co irradiation

Purpose: The aim of this study was to identify gene expression profiles distinguishing alpha-particle At-211 and Co-60 irradiation. Materials and methods: Gene expression microarray profiling was performed using total RNA from confluent human fibroblasts 5 hours after exposure to 211 At labeled trastuzumab monoclonal antibody (0.25, 0.5, and 1 Gy) and Co-60 (1, 2, and 3 Gy). Results: We report gene expression profiles that distinguish the effect different radiation qualities and absorbed doses have on cellular functions in human fibroblasts. In addition, we identified commonly expressed transcripts between At-211 and Co-60 irradiation. A greater number of transcripts were modulated by 211 At than Co-60 irradiation. In addition, down-regulation was more prevalent than up-regulation following 211 At irradiation. Several biological processes were enriched for both irradiation qualities such as transcription, cell cycle regulation, and cell cycle arrest, whereas mitosis, spindle assembly checkpoint, and apoptotic chromosome condensation were uniquely enriched for alpha particle irradiation. Conclusions: LET-dependent transcriptional modulations were observed in human fibroblasts 5 hours after irradiation exposure. These findings suggest that in comparison with Co-60, At-211 has the clearest influence on both tumor protein p53-activated and repressed genes, which impose a greater overall burden to the cell following alpha particle irradiation.