Bystander-mediated genomic instability after high LET radiation in murine primary haemopoietic stem cells.
Communication between irradiated and unirradiated (bystander) cells can result in responses in unirradiated cells that are similar to responses in their irradiated counterparts. The purpose of the current experiment was to test the hypothesis that bystander responses will be similarly induced in primary murine stem cells under different cell culture conditions. The experimental systems used here, co-culture and media transfer, are similar in that they both restrict communication between irradiated and bystander cells to media borne factors, but are distinct in that with the media transfer technique, cells can only communicate after irradiation, and with co-culture, cells can communication before, during and after irradiation. In this set of parallel experiments, cell type, biological endpoint, and radiation quality and dose, were kept constant. In both experimental systems, clonogenic survival was significantly decreased in all groups, whether irradiated or bystander, suggesting a substantial contribution of bystander effects (BE) to cell killing. Genomic instability (GI) was induced under all radiation and bystander conditions in both experiments, including a situation where unirradiated cells were incubated with media that had been conditioned for 24h with irradiated cells. The appearance of delayed aberrations (genomic instability) 10-13 population doublings after irradiation was similar to the level of initial chromosomal damage, suggesting that the bystander factor is able to induce chromosomal alterations soon after irradiation. Whether these early alterations are related to those observed at later timepoints remains unknown. These results suggest that genomic instability may be significantly induced in a bystander cell population whether or not cells communicate during irradiation.
Bowler
Deborah A
DA
Radiation and Genome Stability Unit, Medical Research Council, Harwell, Didcot Oxfordshire OX11 0RD, UK.
Moore
Stephen R
SR
Macdonald
Denise A
DA
Smyth
Sharon H
SH
Clapham
Peter
P
Kadhim
Munira A
MA
D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned; D004249:DNA Damage; D042822:Genomic Instability / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000528:radiation effects*; D018499:Linear Energy Transfer; D051379:Mice
D017077:Culture Media, Conditioned