title: Effects of very low fluences of high-energy protons or iron ions on irradiated and bystander cells.
abstract: In space, astronauts are exposed to radiation fields consisting of energetic protons and high atomic number, high-energy (HZE) particles at very low dose rates or fluences. Under these conditions, it is likely that, in addition to cells in an astronaut's body being traversed by ionizing radiation particles, unirradiated cells can also receive intercellular bystander signals from irradiated cells. Thus this study was designed to determine the dependence of DNA damage induction on dose at very low fluences of charged particles. Novel techniques to quantify particle fluence have been developed at the NASA Space Radiation Biology Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The approach uses a large ionization chamber to visualize the radiation beam coupled with a scintillation counter to measure fluence. This development has allowed us to irradiate cells with 1 GeV/nucleon protons and iron ions at particle fluences as low as 200 particles/cm(2) and quantify biological responses. Our results show an increased fraction of cells with DNA damage in both the irradiated population and bystander cells sharing medium with irradiated cells after low fluences. The fraction of cells with damage, manifest as micronucleus formation and 53BP1 focus induction, is about 2-fold higher than background at doses as low as ∼0.47 mGy iron ions (∼0.02 iron ions/cell) or ∼70 μGy protons (∼2 protons/cell). In the irradiated population, irrespective of radiation type, the fraction of damaged cells is constant from the lowest damaging fluence to about 1 cGy, above which the fraction of damaged cells increases with dose. In the bystander population, the level of damage is the same as in the irradiated population up to 1 cGy, but it does not increase above that plateau level with increasing dose. The data suggest that at fluences of high-energy protons or iron ions less than about 5 cGy, the response in irradiated cell populations may be dominated by the bystander response.
authors: Department of Radiation Oncology, Cox 302, 55 Fruit Street, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.
authors: H
authors: H
authors: Yang
authors: N
authors: N
authors: Magpayo
authors: A
authors: A
authors: Rusek
authors: I-H
authors: IH
authors: Chiang
authors: M
authors: M
authors: Sivertz
authors: K D
authors: KD
authors: Held
mesh_terms: D024201:Bystander Effect / Q000528:radiation effects*; D002412:Cations / Q000009:adverse effects; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007501:Iron / Q000009:adverse effects*; D015162:Micronucleus Tests; D011522:Protons / Q000009:adverse effects*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D002412:Cations; C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D011522:Protons; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D007501:Iron