title: Long-lived inflammatory signaling in irradiated bone marrow is genome dependent.
abstract: Ionizing radiation is carcinogenic, but genotype is a key determinant of susceptibility. Mutational DNA damage is generally attributed to cause disease, but irradiation also affects multicellular interactions as a result of poorly understood bystander effects that may influence carcinogenic susceptibility. In this study, we show that the bone marrow of irradiated mice will retain the ability to kill hemopoietic clonogenic stem cells and to induce chromosomal instability for up to 3 months after irradiation. Chromosomal instability was induced in bone marrow cells derived from CBA/Ca mice, a strain that is susceptible to radiation-induced acute myeloid leukemia (r-AML), but not in C57BL6 mice that are resistant to r-AML. Similarly, clonogenic cell lethality was exhibited in C57BL/6 mice but not CBA/Ca mice. Mechanistic investigations revealed that these genotype-dependent effects involved cytokine-mediated signaling and were mediated by a cyclooxygenase-2-dependent mechanism. Thus, our results suggested that inflammatory processes were responsible for mediating and sustaining the durable effects of ionizing radiation observed on bone marrow cells. Because most exposures to ionizing radiation are directed to only part of the body, our findings imply that genotype-directed tissue responses may be important determinants of understanding the specific consequence of radiation exposure in different individuals.
authors: University of Dundee Medical School, Centre for Oncology and Molecular Medicine, Scotland, United Kingdom.
authors: Sally A
authors: SA
authors: Lorimore
authors: Debayan
authors: D
authors: Mukherjee
authors: Joanne I
authors: JI
authors: Robinson
authors: Jennifer A
authors: JA
authors: Chrystal
authors: Eric G
authors: EG
authors: Wright
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D024201:Bystander Effect / Q000235:genetics / Q000528:radiation effects; D043171:Chromosomal Instability / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects
chemical_list: D016207:Cytokines; D051546:Cyclooxygenase 2