Targeted and non-targeted effects from combinations of low doses of energetic protons and iron ions in human fibroblasts

Purpose: In space, astronauts are exposed to mixed radiation fields consisting of energetic protons and high atomic number, high energy (HZE) particles at low dose rates. Therefore, it is critical to understand effects of combinations of low doses of different radiation types at the cellular level. Materials and methods: AG01522 normal human skin fibroblasts and a transwell insert co-culture system were used. Irradiations used were 1 GeV/amu (gigaelectron volt/atomic mass unit) protons and 1 GeV/amu iron (Fe) ions. DNA damage was measured as micronucleus (MN) formation and p53 binding protein 1 (53BP1) foci induction. Results: The same magnitude of DNA damage was induced in cells sequentially exposed to 1 cGy protons and 1 cGy Fe ions as in cells irradiated with either protons or Fe ions alone. The same magnitude of DNA damage was also observed in non-irradiated bystander cells sharing medium with cells irradiated with either 1 cGy protons or iron ions or protons plus iron ions. However, when the 'bystander' cells were exposed to 1 cGy protons up to 3 h before co-culture with Fe ion-irradiated cells, no DNA damage in the 'bystander' cells was observed. Conclusions: These data provide the first evidence of interactions between targeted and non-targeted DNA damage caused by dual exposure to low doses of energetic protons and iron ions.