title: Genomic instability in human lymphocytes irradiated with individual charged particles: involvement of tumor necrosis factor alpha in irradiated cells but not bystander cells.
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 alpha 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 alpha (TNFA). Genomic instability was significantly elevated in irradiated groups (> or = two-fold 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.
authors.affiliation: Radiation and Genome Stability Unit, Medical Research Council, Harwell, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Moore
authors.forename: Sam
authors.initials: S
authors.lastname: Marsden
authors.forename: Denise
authors.initials: D
authors.lastname: Macdonald
authors.forename: Stephen
authors.initials: S
authors.lastname: Mitchell
authors.forename: Melvyn
authors.initials: M
authors.lastname: Folkard
authors.forename: Barry
authors.initials: B
authors.lastname: Michael
authors.forename: Dudley T
authors.initials: DT
authors.lastname: Goodhead
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
authors.forename: Munira A
authors.initials: MA
authors.lastname: Kadhim
mesh_terms: D024201:Bystander Effect / Q000235:genetics* / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects; D002875:Chromosomes / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D015894:Genome, Human; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D011829:Radiation Dosage; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha