Transcriptional responses in irradiated and bystander fibroblasts after low dose α-particle radiation.

PURPOSE: The objective of this study was to demonstrate the radiation-induced bystander effect (RIBE) in human F11 fibroblasts using micronucleus (MN) formation as an end-point and to investigate transcriptional responses towards low doses of α-particle radiation in irradiated and bystander fibroblasts employing genome-wide microarray analysis.

MATERIALS AND METHODS: The MN frequency was investigated in unirradiated bystander cells recipient of growth medium from α-particle irradiated (0, 0.1, 0.5 and 2 Gy) immortalized human F11 fibroblasts. The irradiated conditioned medium (ICM) was transferred from irradiated to bystander fibroblasts 2 h after irradiation. Microarray analysis was performed in 0.1 Gy α-particle irradiated cells, unirradiated bystander cells and appropriate controls at different time points after ICM transfer. Microarray data analysis was performed at the single-gene level and gene-set level.

RESULTS: MN were induced in unirradiated fibroblasts recipient of ICM harvested from 0.1 Gy α-particle irradiated cultures, but not from cultures irradiated with 0.5 or 2 Gy. Fibroblasts irradiated with 0.1 Gy showed repression of 26 genes 4 h after being irradiated. However, no significantly altered genes were found in bystander fibroblasts at any of the time points used in this study. Gene-set enrichment analysis showed that pathways such as ribosome, protein export, proteasome and protein 53 (p53) signaling were enriched in irradiated cells. However, bystander cells were enriched only in the lysosome pathway 24 h after receiving ICM, indicating persistence of the signals received from the irradiated cells.

CONCLUSION: MN formation was induced in bystander fibroblast receiving medium from 0.1 Gy α-particle irradiated fibroblasts, but this was accompanied with only minor transcriptional responses.