The in vivo expression of radiation-induced chromosomal instability has an inflammatory mechanism

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

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)18-24
    Number of pages7
    JournalRadiation Research
    Volume177
    Issue number1
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    Chromosomal Instability
    Radiation
    phenotype
    radiation
    damage
    DNA Damage
    mice
    deoxyribonucleic acid
    cells
    Phenotype
    chromosome aberrations
    leukemias
    Radiation Effects
    radiation effects
    Ionizing Radiation
    Cell Nucleus
    Acute Myeloid Leukemia
    Chromosome Aberrations
    ionizing radiation
    markers

    Cite this

    Mukherjee, Debayan ; Coates, Philip J. ; Lorimore, Sally A. ; Wright, Eric G. / The in vivo expression of radiation-induced chromosomal instability has an inflammatory mechanism. In: Radiation Research. 2012 ; Vol. 177, No. 1. pp. 18-24.
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    The in vivo expression of radiation-induced chromosomal instability has an inflammatory mechanism. / Mukherjee, Debayan; Coates, Philip J.; Lorimore, Sally A.; Wright, Eric G.

    In: Radiation Research, Vol. 177, No. 1, 2012, p. 18-24.

    Research output: Contribution to journalArticle

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    T1 - The in vivo expression of radiation-induced chromosomal instability has an inflammatory mechanism

    AU - Mukherjee, Debayan

    AU - Coates, Philip J.

    AU - Lorimore, Sally A.

    AU - Wright, Eric G.

    PY - 2012

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    AB - 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.

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