Radiation-induced bone marrow apoptosis, inflammatory bystander-type signaling and tissue cytotoxicity.
OBJECTIVE
A study of irradiated (0.25-2 Gy) murine bone marrow has investigated the relationships between apoptotic responses of cells exposed in vivo and in vitro and between in vivo apoptosis and tissue cytotoxicity.


METHODS
The time course of reduction in bone marrow cellularity in vivo was determined by femoral cell counts and apoptosis measurements obtained using three commonly used assays. Inflammatory pro-apoptotic cytokine production at 24 h post-exposure in vivo was investigated using a bystander protocol.


RESULTS
In vivo, there is a dose- and time-dependent non-linear reduction in bone marrow cellularity up to 24 h post- irradiation not directly represented by apoptosis measurements. The majority of cells are killed within 6 h but there is on-going cell loss in vivo up to 24 h post-irradiation in the absence of elevated levels of apoptosis and associated with the induction of cytokines produced in response to the initial tumor protein 53 (p53)-dependent apoptosis.


CONCLUSIONS
The results demonstrate that small increases in measured apoptosis can reflect significant intramedullary cell death and with apoptotic processes being responsible for pro-inflammatory mechanisms that can contribute to additional on-going cell death. The findings demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures.
Centre for Oncology and Molecular Medicine University of Dundee Medical School, Dundee, Scotland, UK.
Debayan
D
Mukherjee
Philip J
PJ
Coates
Shubhra
S
Rastogi
Sally A
SA
Lorimore
Eric G
EG
Wright
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology* / Q000528:radiation effects*; D024201:Bystander Effect / Q000528:radiation effects; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects; D016158:Genes, p53; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology / Q000528:radiation effects; D057170:Translational Research, Biomedical
D016207:Cytokines; D018836:Inflammation Mediators