A.2 BIOLOGICAL RESPONSES AT LOW DOSES
A variety of different biological responses have been identified at low doses of radiation, although it is difficult to identify effects at doses that are close to those encountered from natural background radiation. It is highly unlikely that epidemiologic studies of populations around nuclear facilities will contribute toward knowledge of the effects of radiation at very low doses. Because of the epidemiologic limitations, efforts are directed toward improving understanding of the effects, response, and defense mechanisms to low-dose radiation at the cellular and molecular levels. The Department of Energy’s Low Dose Radiation Program is focused on understanding the effects of doses of radiation under 100 mSv by supporting research of the molecular and cellular responses to very-low-dose exposures. Some scientists have argued that DNA repair capabilities are effective at low doses, preventing the accumulation of DNA damage and mutations following low-dose exposures, while others have argued that low doses may be even more damaging per unit dose than high doses.
Major discussion on the biological consequences of low-dose radiation despite being controversial has also led to the identification of pathways of radiation damage that are evident at low doses but difficult to measure at high doses in light of overwhelming DNA damage. Among these is the adaptive response, which would tend to dampen the potential adverse effects and perhaps even provide a beneficial (or hormetic) effect of radiation exposure at low doses. In most studies of adaptive responses, cells in vitro are given a “tickle” low dose of radiation (for example 20 cGy or 0.2 Gy) followed by a high dose of radiation (1 Gy). The administration of the “tickle” dose prevents some of the damaging effects of the high dose, including cell killing and chromosomal injury. In animal models a variety of investigators have documented that low doses of radiation can enhance immune responses (Cheng et al., 2010).
There are also several damaging responses observed at low doses, including the bystander effect and delayed genomic instability. The bystander effect is defined as genetic changes (chromosome damage, mutations) induced in cells that are not directly hit by the radiation beam. The exact mechanism by which the bystander effect occurs is unclear, although data support both transmission of a factor either in conditioned medium (Sowa Resat and Morgan, 2004) or through gap junctions (Gaillard et al., 2009). Recent studies have documented that such bystander effects may occur in vivo as well (Singh et al., 2011). Delayed genomic instability has also been identified in irradiated cell populations where mutations do not occur in the irradiated cells themselves but rather in the progeny of these irradiated cells sometimes up to 13 generations later (Little et al., 1997; Morgan, 2003).
Another detrimental effect of low-dose exposures (mostly in the cGy range) is low-dose hypersensitivity in which some cells in culture show an