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

Abstract

Purpose: The aim of this study was to identify gene expression profiles distinguishing alpha-particle ²¹¹At and ⁶⁰Co irradiation.

Materials and methods: Gene expression microarray profiling was performed using total RNA from confluent human fibroblasts 5 hours after exposure to ²¹¹At labeled trastuzumab monoclonal antibody (0.25, 0.5, and 1 Gy) and ⁶⁰Co (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 ²¹¹At and ⁶⁰Co irradiation. A greater number of transcripts were modulated by ²¹¹At than ⁶⁰Co irradiation. In addition, down-regulation was more prevalent than up-regulation following ²¹¹At 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 ⁶⁰Co, ²¹¹At 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.

Keywords::

• Alpha emitters
• High-LET
• molecular radiobiology
• gene expression
• human fibroblast

Acknowledgements

The authors thank Sture Lindegren for distillation and labeling of ²¹¹At and Ulla Delle for flow cytometric analysis.

Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by the King Gustav V Jubilee Clinic Cancer Research Foundation.