Expression profiles are different in carbon ion-irradiated normal human fibroblasts and their bystander cells

Iwakawa, Mayumi*; Hamada, Nobuyuki*; Imadome, Kaori*; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko; Imai, Takashi*

We performed microarray analysis of irradiated and bystander fibroblasts in confluent cultures. To see the effects in bystander cells, each of 1, 5 and 25 sites was targeted with 10 particles of carbon ions using microbeams, where particles traversed 0.00026, 0.0013 and 0.0066% of cells, respectively. To see the effects in irradiated cells, cultures were exposed to 10% survival dose (D), 0.1D and 0.01D of corresponding broadbeams. Irrespective of the target numbers (1, 5 or 25 sites) and the time (2 or 6 h postirradiation), similar expression changes were observed in bystander cells. Among 874 probes that showed more than 1.5-fold changes in bystander cells, 25% were upregulated and the remainder downregulated. These included genes related to cell communication, stress response and cell cycle. Pathway analysis revealed serial bystander activation of G protein/PI-3 kinase pathways. Instead, genes related to cell cycle or death and cell communication were upregulated in irradiated cells, but not in bystander cells. Our results indicate different expression profiles in irradiated and bystander cells, and imply that intercellular signaling between irradiated and bystander cells activate intracellular signaling, leading to the transcriptional stress response in bystander cells.