Radiation-induced delayed bystander-type effects mediated by hemopoietic cells.
Genetic lesions and cell death associated with exposure to ionizing radiation have generally been attributed to DNA damage arising as a consequence of deposition of energy in the cell nucleus. However, reports of radiation-induced bystander effects, in which DNA damage is produced in nonirradiated cells as a consequence of communication with irradiated cells, indicate additional mechanisms. At present, most information has been obtained using in vitro systems, and the in vivo significance of bystander factors is not clear. In this study we show that signals generated in vivo in the bone marrow of CBA/Ca mice irradiated with 4 Gy gamma rays 24 h previously, but not immediately postirradiation, are able to induce DNA damage and apoptosis in nonirradiated bone marrow cells. The signaling mechanism involves FasL, TNF-alpha, nitric oxide and superoxide and macrophages are implicated as a source of damaging signals. Such delayed bystander-type damage demonstrates the importance of studying tissue responses subsequent to the radiation exposure as well as effects at the time of irradiation when considering the mechanisms underlying the consequences of radiation exposures.
Centre for Oncology and Molecular Medicine, University of Dundee Medical School, Scotland, United Kingdom.
Karen L
KL
Burr
Joanne I
JI
Robinson
Shubhra
S
Rastogi
Michael T
MT
Boylan
Philip J
PJ
Coates
Sally A
SA
Lorimore
Eric G
EG
Wright
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D024201:Bystander Effect / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D053222:Fas Ligand Protein / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053222:Fas Ligand Protein; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide