X-irradiation and bystander effects induce similar changes of transcript profiles in most functional pathways in...

Unirradiated cells which neighbor cells exposed to ionizing radiation (IR) show responses termed bystander effects, including DNA damage, chromosomal instability, mutation, and apoptosis. We used genome-wide microarrays to compare the change in transcript profiles in Me45 (human melanoma) cells grown in culture medium from irradiated cells (irradiation conditioned medium, ICM) with those which occurred after IR, sampling after more than one division cycle to detect long-term changes which could be relevant in radiotherapy. Transcripts of >10,000 genes showed an increased or decreased level in both conditions using the criterion of a >+/-10% change, and >85% of these were common to growth in ICM and after IR. When these genes were grouped into metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes (KEGG), significant differences (p<0.01) were seen between the numbers of up- and down-regulated transcripts in certain groups after both ICM and IR, particularly in the groups neuroactive ligand-receptor interactions, oxidative phosphorylation, cytokine-cytokine receptor interactions, proteasomes, and ribosomes. Quantitative RT-PCR assays of transcripts of selected genes in these pathways confirmed the similar effects of growth in ICM and IR. We conclude that factors transmitted from irradiated cells can influence transcript levels in bystander cells, and that these changes persist for more than one cell cycle consistent with the long-term transmissible effects seen in progeny cells, revealing new facets of the IR-induced bystander effect.