Genomic instability in human lymphocytes irradiated with individual charged particles: Involvement of tumor necrosis factor α in irradiated cells but not bystander cells

Stephen Moore, Sam Marsden, Denise Macdonald, Stephen Mitchell, Melvyn Folkard, Barry Michael, Dudley T. Goodhead, Kevin M. Prise, Munira A. Kadhim

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Exposure to ionizing radiation can increase the risk of cancer, which is often characterized by genomic instability. In environmental exposures to high-LET radiation (e.g. 222Ra), it is unlikely that many cells will be traversed or that any cell will be traversed by more than one α particle, resulting in an in vivo bystander situation, potentially involving inflammation. Here primary human lymphocytes were irradiated with precise numbers of 3He2+ ions delivered to defined cell population fractions, to as low as a single cell being traversed, resembling in vivo conditions. Also, we assessed the contribution to genomic instability of the pro-inflammatory cytokine tumor necrosis factor α (TNFA). Genomic instability was significantly elevated in irradiated groups (≥twofold over controls) and was comparable whether cells were traversed by one or two 3He2+ ions. Interestingly, substantial heterogeneity in genomic instability between experiments was observed when only one cell was traversed. Genomic instability was significantly reduced (60%) in cultures in which all cells were irradiated in the presence of TNFA antibody, but not when fractions were irradiated under the same conditions, suggesting that TNFA may have a role in the initiation of genomic instability in irradiated cells but not bystander cells. These results have implications for low-dose exposure risks and cancer.

Original languageEnglish (US)
Pages (from-to)183-190
Number of pages8
JournalRadiation Research
Volume163
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

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tumor necrosis factors
necrosis
Genomic Instability
lymphocytes
charged particles
tumors
Tumor Necrosis Factor-alpha
Lymphocytes
genomics
cells
cancer
Ions
ions
Linear Energy Transfer
antibodies
ionizing radiation
neoplasms
Environmental Exposure
Ionizing Radiation
Neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Genomic instability in human lymphocytes irradiated with individual charged particles : Involvement of tumor necrosis factor α in irradiated cells but not bystander cells. / Moore, Stephen; Marsden, Sam; Macdonald, Denise; Mitchell, Stephen; Folkard, Melvyn; Michael, Barry; Goodhead, Dudley T.; Prise, Kevin M.; Kadhim, Munira A.

In: Radiation Research, Vol. 163, No. 2, 02.2005, p. 183-190.

Research output: Contribution to journalArticle

Moore, Stephen ; Marsden, Sam ; Macdonald, Denise ; Mitchell, Stephen ; Folkard, Melvyn ; Michael, Barry ; Goodhead, Dudley T. ; Prise, Kevin M. ; Kadhim, Munira A. / Genomic instability in human lymphocytes irradiated with individual charged particles : Involvement of tumor necrosis factor α in irradiated cells but not bystander cells. In: Radiation Research. 2005 ; Vol. 163, No. 2. pp. 183-190.
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