Comparison of transcriptional profiles in human lymphocyte cells irradiated with 12C ion beams at 0-2.0 Gy

Abstract

Objective: Heavy ions have contributed to tumor site-specific radiotherapy and are a major health risk for astronauts. The purpose of this study was to investigate the changes in gene expression in peripheral lymphocytes of cancer patients and astronauts exposed to 12C ions, and identify suitable molecular biomarkers for health monitoring. We also aimed to observe the effects of treatment and the level of damage, by comparing the transcriptional profiles of human lymphocyte cell lines exposed to 12C ion beams at doses of 0-2.0 Gy. Materials and methods: A human lymphocyte cell line was irradiated with 12C ion beams at 0, 0.1, 0.5, and 2.0 Gy and transcriptional profiles were evaluated using the Agilent human gene expression microarray at 24 hours after irradiation. Differentially expressed genes were identified using a fold change of =2.0. Representative genes were further validated by RT-PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to determine the roles of differentially expressed mRNAs. Results: Based on the microarray assays, 1,113 genes were upregulated and 853 genes were downregulated in human lymphocyte cells irradiated with 0.1 Gy 12C ion beams compared with the control group, 1,095 genes were upregulated and 1,220 genes were downregulated in cells irradiated with 0.5 Gy 12C ion beams, and 1,055 genes were upregulated and 1,356 genes were downregulated in cells irradiated with 2.0 Gy. A total of 504 genes were differentially expressed in all irradiated groups, of which 88 genes were upregulated and 416 genes downregulated. Most of these altered genes were related to the cell cycle, apoptosis, signal transduction, DNA transcription, repair, and replication. The expression differences were further confirmed by RT-PCR for a subset of differentially expressed genes. Conclusion: Differentially expressed genes between treatment and control groups at 24 hours post-irradiation increased as the radiation dose increased; upregulated genes gradually decreased and downregulated genes increased. Our data indicated that 12C ion beams could repress a number of genes in a dose-dependent manner, which might lead to the failure of multiple cellular biological functions.