title: The in vivo expression of radiation-induced chromosomal instability has an inflammatory mechanism.
abstract: Ionizing radiation is unequivocally leukemogenic and carcinogenic, and this is generally attributed to DNA damage arising as a consequence of deposition of energy in the cell nucleus at the time of exposure. However, nontargeted effects, in which DNA damage is produced in nonirradiated cells as a consequence of cell signaling processes, indicate additional mechanisms. Radiation-induced chromosomal instability, a nontargeted effect with the potential to produce pathological consequences, is characterized by an increased rate of chromosome aberrations many generations after the initial insult. In this study, using a mouse model that has been well characterized with respect to its susceptibility to both radiation-induced chromosomal instability and acute myeloid leukemia, we investigated whether the underlying signaling mechanism was an inflammatory process by studying the effects of a nonsteroidal anti-inflammatory drug. Treated mice showed significant reduction in expression of the chromosomal instability phenotype 100 days postirradiation associated with reduced expression of inflammatory markers. The data support the hypothesis that the radiation-induced chromosomal instability phenotype is not an intrinsic property of the cells but a consequence of inflammatory processes having the potential to contribute secondary damage expressed as nontargeted and delayed radiation effects.
authors: University of Dundee, Centre for Oncology and Molecular Medicine, Division of Medical Science, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom DD1 9SY.
authors: Debayan
authors: D
authors: Mukherjee
authors: Philip J
authors: PJ
authors: Coates
authors: Sally A
authors: SA
authors: Lorimore
authors: Eric G
authors: EG
authors: Wright
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D000068579:Celecoxib; D043171:Chromosomal Instability / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects*; D007249:Inflammation / Q000235:genetics; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib