Bystander effects induced by medium from irradiated cells: similar transcriptome responses in irradiated and bystander K562 cells.
OBJECTIVE
Cells exposed to ionizing radiation release factors that induce deoxyribonucleic acid damage, chromosomal instability, apoptosis, and changes in the proliferation rate of neighboring unexposed cells, phenomena known as bystander effects. This work analyzes and compares changes in global transcript levels induced by direct irradiation and by bystander effects in K562 (human erythroleukemia) cells.


METHODS
Cells were X-irradiated with 4 Gy or transferred into culture medium collected from cells 1 h after irradiation (irradiation-conditioned medium). Global transcript profiles were assessed after 36 h of growth by use of Affymetrix microarrays (Affymetrix, Santa Clara, CA) and the kinetics of change of selected transcripts by quantitative reverse transcriptase-polymerase chain reaction.


RESULTS
The level of the majority (72%) of transcripts changed similarly (increase, decrease, or no change) in cells grown in irradiation-conditioned medium or irradiated, whereas only 0.6% showed an opposite response. Transcript level changes in bystander and irradiated cells were significantly different from those in untreated cells grown for the same amount of time and were confirmed by quantitative reverse transcriptase-polymerase chain reaction for selected genes. Signaling pathways in which the highest number of transcripts changed in both conditions were found in the following groups: neuroactive ligand-receptor, cytokine-cytokine receptor interaction, Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) and Mitogen-Activated Protein Kinase (MAPK) In control cells more transcripts were downregulated than in irradiated and bystander cells with transcription factors YBX1 and STAT5B, heat shock protein HSPA1A, and ribonucleic acid helicase DDX3X as examples.


CONCLUSIONS
The transcriptomes of cells grown in medium from X-irradiated cells or directly irradiated show very similar changes. Signals released by irradiated cells may cause changes in the transcriptome of neighboring cells that sustain their survival.
Herok
Robert
R
Department of Experimental and Clinical Radiobiology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
Konopacka
Maria
M
Polanska
Joanna
J
Swierniak
Andrzej
A
Rogolinski
Jacek
J
Jaksik
Roman
R
Hancock
Ronald
R
Rzeszowska-Wolny
Joanna
J
D024201:Bystander Effect / Q000187:drug effects / Q000528:radiation effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004249:DNA Damage; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020014:K562 Cells / Q000378:metabolism / Q000528:radiation effects*; D011829:Radiation Dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects*; D013997:Time Factors; D015854:Up-Regulation
D017077:Culture Media, Conditioned