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.

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

“…Other lines of evidence for bystander effects at low doses of HZE particles include the appearance of DNA damage foci in several recent reports (36,37). Several lines of evidence suggest that d rays are not responsible for the deviation from linearity observed for simple exchanges at low doses of HZE particles.…”

Functional Consequences of Radiation-Induced Oxidative Stress in Cultured Neural Stem Cells and the Brain Exposed to Charged Particle Irradiation

“…The counter is 1 cm 2 and can accept up to about 10 5 counts/spill, while the beam can be reduced to 10 2 ions/cm 2 per spill, thereby providing a useful method for measuring dose over the low ion fluences used in this study. The NSRL physics staff performed all dosimetry and further details regarding similar dosimetry setups have been published (53).…”

Radiation quality-dependence of bystander effect in unirradiated fibroblasts is associated with TGF-β1-Smad2 pathway and miR-21 in irradiated keratinocytes

“…in unirradiated cells when the neighboring cells are traversed by ionizing radiation. So far, although RIBE has been demonstrated in various types of cells exposed to different types of radiation2345678910, it is still controversial whether RIBE is a universal phenomenon1112. In addition to the proposed factors such as the epigenetic status of a specific cell line, the precise culture conditions, medium supplements and appropriate endpoint detected at appropriate time111213, radiation quality may be another factor that is critical to the occurrence of RIBE.…”