Abstract:
:Untargeted effects of ionizing radiation (de novo effects in the unirradiated descendants or neighbors of irradiated cells) challenge widely held views about the mechanisms of radiation-induced DNA damage with implications for the health consequences of radiation exposures particularly in the context of the induction of malignancy. To investigate in vivo untargeted effects of sparsely ionizing (low linear energy transfer) radiation, a congenic sex-mismatch bone marrow transplantation protocol has been used to repopulate the hemopoietic system from a mixture of gamma-irradiated and nonirradiated hemopoietic stem cells such that host-, irradiated donor- and unirradiated donor-derived cells can be distinguished. Chromosomal instability in the progeny of irradiated hemopoietic stem cells accompanied by a reduction in their contribution to the repopulated hemopoietic system is consistent with a delayed genomic instability phenotype being expressed in vivo. However, chromosomal instability was also shown in the progeny of the nonirradiated hemopoietic stem cells implicating a bystander mechanism. Studies of the influence of irradiated recipient stromal microenvironment and experiments replacing irradiated cells with irradiated cell-conditioned medium reveal the source of the in vivo bystander effect to be the descendants of irradiated cells, rather than irradiated cell themselves. Thus, it is possible that a radiation-induced genomic instability phenotype in vivo need not necessarily be a reflection of intrinsically unstable cells but the responses to ongoing production of inflammatory-type damaging signals as a long-term unexpected consequence of the initial single radiation exposure.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lorimore SA,McIlrath JM,Coates PJ,Wright EGdoi
10.1158/0008-5472.CAN-05-0834subject
Has Abstractpub_date
2005-07-01 00:00:00pages
5668-73issue
13eissn
0008-5472issn
1538-7445pii
65/13/5668journal_volume
65pub_type
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