title: Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions.
abstract: During interplanetary missions, astronauts are exposed to mixed types of ionizing radiation. The low 'flux' of the high atomic number and high energy (HZE) radiations relative to the higher 'flux' of low linear energy transfer (LET) protons makes it highly probable that for any given cell in the body, proton events will precede any HZE event. Whereas progress has been made in our understanding of the biological effects of low-LET protons and high-LET HZE particles, the interplay between the biochemical processes modulated by these radiations is unclear. Here we show that exposure of normal human fibroblasts to a low mean absorbed dose of 20 cGy of 0.05 or 1-GeV protons (LET ∼ 1.25 or 0.2 keV/μm, respectively) protects the irradiated cells (P < 0.0001) against chromosomal damage induced by a subsequent exposure to a mean absorbed dose of 50 cGy from 1 GeV/u iron ions (LET ∼ 151 keV/μm). Surprisingly, unirradiated (i.e. bystander) cells with which the proton-irradiated cells were co-cultured were also significantly protected from the DNA-damaging effects of the challenge dose. The mitigating effect persisted for at least 24 h. These results highlight the interactions of biological effects due to direct cellular traversal by radiation with those due to bystander effects in cell populations exposed to mixed radiation fields. They show that protective adaptive responses can spread from cells targeted by low-LET space radiation to bystander cells in their vicinity. The findings are relevant to understanding the health hazards of space travel.
authors: Department of Radiology, New Jersey Medical School Cancer Center, Rutgers University, 205 South Orange Avenue, Newark, NJ 07103, USA Present address: Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
authors: Manuela
authors: M
authors: Buonanno
authors: Department of Radiology, New Jersey Medical School Cancer Center, Rutgers University, 205 South Orange Avenue, Newark, NJ 07103, USA.
authors: Sonia M
authors: SM
authors: De Toledo
authors: Department of Radiology, New Jersey Medical School Cancer Center, Rutgers University, 205 South Orange Avenue, Newark, NJ 07103, USA.
authors: Roger W
authors: RW
authors: Howell
authors: Department of Radiology, New Jersey Medical School Cancer Center, Rutgers University, 205 South Orange Avenue, Newark, NJ 07103, USA edouard.azzam@rutgers.edu.
authors: Edouard I
authors: EI
authors: Azzam
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology* / Q000528:radiation effects; D024201:Bystander Effect / Q000502:physiology* / Q000528:radiation effects; D002460:Cell Line; D004249:DNA Damage / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects; D020450:Heavy Ions; D006801:Humans; D007501:Iron; D011522:Protons; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology / Q000528:radiation effects
chemical_list: D011522:Protons; D007501:Iron
keywords: adaptive protection; bystander effect; high atomic number and high energy (HZE) particles; protons; space radiation protection