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

Stephen R. 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

43 Scopus citations

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 1 2005

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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