Radiation-induced bone marrow apoptosis, inflammatory bystander-type signaling and tissue cytotoxicity

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

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Purpose: A study of irradiated (0.25-2 Gy) murine bone marrow has investigated the relationships between apoptotic responses of cells exposed in vivo and in vitro and between in vivo apoptosis and tissue cytotoxicity. Materials and methods: The time course of reduction in bone marrow cellularity in vivo was determined by femoral cell counts and apoptosis measurements obtained using three commonly used assays. Inflammatory pro-apoptotic cytokine production at 24 h post-exposure in vivo was investigated using a bystander protocol. Results: In vivo, there is a dose- and time-dependent non-linear reduction in bone marrow cellularity up to 24 h post- irradiation not directly represented by apoptosis measurements. The majority of cells are killed within 6 h but there is on-going cell loss in vivo up to 24 h post-irradiation in the absence of elevated levels of apoptosis and associated with the induction of cytokines produced in response to the initial tumor protein 53 (p53)-dependent apoptosis. Conclusion: The results demonstrate that small increases in measured apoptosis can reflect significant intramedullary cell death and with apoptotic processes being responsible for pro-inflammatory mechanisms that can contribute to additional on-going cell death. The findings demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures.
    Original languageEnglish
    JournalInternational Journal of Radiation Biology
    DOIs
    Publication statusPublished - 2012

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    Bone Marrow
    Radiation
    Apoptosis
    Cell Death
    Cytokines
    Thigh
    Pyroptosis
    Cell Count
    Neoplasms
    Proteins

    Cite this

    Mukherjee, Debayan ; Coates, Philip J ; Rastogi, Shubhra ; Lorimore, Sally A ; Wright, Eric G. / Radiation-induced bone marrow apoptosis, inflammatory bystander-type signaling and tissue cytotoxicity. In: International Journal of Radiation Biology. 2012.
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    title = "Radiation-induced bone marrow apoptosis, inflammatory bystander-type signaling and tissue cytotoxicity",
    abstract = "Purpose: A study of irradiated (0.25-2 Gy) murine bone marrow has investigated the relationships between apoptotic responses of cells exposed in vivo and in vitro and between in vivo apoptosis and tissue cytotoxicity. Materials and methods: The time course of reduction in bone marrow cellularity in vivo was determined by femoral cell counts and apoptosis measurements obtained using three commonly used assays. Inflammatory pro-apoptotic cytokine production at 24 h post-exposure in vivo was investigated using a bystander protocol. Results: In vivo, there is a dose- and time-dependent non-linear reduction in bone marrow cellularity up to 24 h post- irradiation not directly represented by apoptosis measurements. The majority of cells are killed within 6 h but there is on-going cell loss in vivo up to 24 h post-irradiation in the absence of elevated levels of apoptosis and associated with the induction of cytokines produced in response to the initial tumor protein 53 (p53)-dependent apoptosis. Conclusion: The results demonstrate that small increases in measured apoptosis can reflect significant intramedullary cell death and with apoptotic processes being responsible for pro-inflammatory mechanisms that can contribute to additional on-going cell death. The findings demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures.",
    author = "Debayan Mukherjee and Coates, {Philip J} and Shubhra Rastogi and Lorimore, {Sally A} and Wright, {Eric G}",
    year = "2012",
    doi = "10.3109/09553002.2013.741280",
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    Radiation-induced bone marrow apoptosis, inflammatory bystander-type signaling and tissue cytotoxicity. / Mukherjee, Debayan; Coates, Philip J; Rastogi, Shubhra; Lorimore, Sally A; Wright, Eric G.

    In: International Journal of Radiation Biology, 2012.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Radiation-induced bone marrow apoptosis, inflammatory bystander-type signaling and tissue cytotoxicity

    AU - Mukherjee, Debayan

    AU - Coates, Philip J

    AU - Rastogi, Shubhra

    AU - Lorimore, Sally A

    AU - Wright, Eric G

    PY - 2012

    Y1 - 2012

    N2 - Purpose: A study of irradiated (0.25-2 Gy) murine bone marrow has investigated the relationships between apoptotic responses of cells exposed in vivo and in vitro and between in vivo apoptosis and tissue cytotoxicity. Materials and methods: The time course of reduction in bone marrow cellularity in vivo was determined by femoral cell counts and apoptosis measurements obtained using three commonly used assays. Inflammatory pro-apoptotic cytokine production at 24 h post-exposure in vivo was investigated using a bystander protocol. Results: In vivo, there is a dose- and time-dependent non-linear reduction in bone marrow cellularity up to 24 h post- irradiation not directly represented by apoptosis measurements. The majority of cells are killed within 6 h but there is on-going cell loss in vivo up to 24 h post-irradiation in the absence of elevated levels of apoptosis and associated with the induction of cytokines produced in response to the initial tumor protein 53 (p53)-dependent apoptosis. Conclusion: The results demonstrate that small increases in measured apoptosis can reflect significant intramedullary cell death and with apoptotic processes being responsible for pro-inflammatory mechanisms that can contribute to additional on-going cell death. The findings demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures.

    AB - Purpose: A study of irradiated (0.25-2 Gy) murine bone marrow has investigated the relationships between apoptotic responses of cells exposed in vivo and in vitro and between in vivo apoptosis and tissue cytotoxicity. Materials and methods: The time course of reduction in bone marrow cellularity in vivo was determined by femoral cell counts and apoptosis measurements obtained using three commonly used assays. Inflammatory pro-apoptotic cytokine production at 24 h post-exposure in vivo was investigated using a bystander protocol. Results: In vivo, there is a dose- and time-dependent non-linear reduction in bone marrow cellularity up to 24 h post- irradiation not directly represented by apoptosis measurements. The majority of cells are killed within 6 h but there is on-going cell loss in vivo up to 24 h post-irradiation in the absence of elevated levels of apoptosis and associated with the induction of cytokines produced in response to the initial tumor protein 53 (p53)-dependent apoptosis. Conclusion: The results demonstrate that small increases in measured apoptosis can reflect significant intramedullary cell death and with apoptotic processes being responsible for pro-inflammatory mechanisms that can contribute to additional on-going cell death. The findings demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures.

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