The influence of p53 functions on radiation-induced inflammatory bystander-type signaling in murine bone marrow.

Sally A Lorimore, Shubhra Rastogi, Debayan Mukherjee, Philip J Coates, Eric G Wright

    Research output: Contribution to journalArticlepeer-review


    Radiation-induced bystander and abscopal effects, in which DNA damage is produced by inter-cellular communication, indicate mechanisms of generating damage in addition to those observed in directly irradiated cells. In this article, we show that the bone marrow of irradiated p53(+/+) mice, but not p53(-/-) mice, produces the inflammatory pro-apoptotic cytokines FasL and TNF-α able to induce p53-independent apoptosis in vitro in nonirradiated p53(-/-) bone marrow cells. Using a congenic sex-mismatch bone marrow transplantation protocol to generate chimeric mice, p53(-/-) hemopoietic cells functioning in a p53(+/+) bone marrow stromal microenvironment exhibited greater cell killing after irradiation than p53(-/-) hemopoietic cells in a p53(-/-) microenvironment. Cytogenetic analysis demonstrated fewer damaged p53(-/-) cells in a p53(+/+) microenvironment than p53(-/-) cells in a p53(-/-) microenvironment. Using the two different model systems, the findings implicate inflammatory tissue processes induced as a consequence of p53-dependent cellular responses to the initial radiation damage, producing cytokines that subsequently induce ongoing p53-independent apoptosis. As inactivation of the p53 tumor suppressor pathway is a common event in malignant cells developing in a stromal microenvironment that has normal p53 function, the signaling processes identified in the current investigations have potential implications for disease pathogenesis and therapy.
    Original languageEnglish
    JournalRadiation Research
    Issue number4
    Publication statusPublished - Apr 2013


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