Low-dose radiation: Thresholds, bystander effects, and adaptive responses

Ionizing radiation fills the universe. Daily ionizing particles and rays collide with molecules in ≈1% of the 100 trillion cells that make up the average human. These collisions generate clusters of free radicals known as reactive oxygen species that randomly damage cellular constituents including DNA (1). Certain types of ionizing radiation are more effective at generating reactive oxygen species; one α-particle is at least 10 times more damaging than one γ-ray. To take these differences into account, the Sievert (Sv), a unit that multiplies the absorbed dose in grays (Gy) by the relative effectiveness of the particle or ray to inflict damage, was developed. On this scale, natural background radiation is ≈0.01 mSv/day, although there are areas on earth that have values 5-fold higher (2), and space-station inhabitants may receive ≈1 mSv/day (3). At the other end of the scale, acute exposures of >150 mSv, a range known as high-dose radiation, have measurable and often serious immediate effects on humans (4). Between background and high-dose radiation is the range of exposures known as low-dose radiation. Low-dose radiation has no immediately noticeable effects on humans; nevertheless there is great interest in its long-term biological effects, which may include cancer in exposed individuals and genetic defects in their progeny.

Research into the biological effects of low-dose radiation exposure is hindered by a lack of assays sensitive enough to measure the relevant cellular alterations. More-sensitive assays are being developed, an important one being the ability to detect the cellular presence of the most serious and potentially lethal type of cellular damage, the DNA double-strand break (DSB). This assay is based on the finding that one of the highly conserved histone proteins that package the DNA into chromatin, H2AX, becomes phosphorylated at the sites of nascent DNA DSBs (5–8). The response is …