Biologic responses to low doses of ionizing radiation: adaptive response versus bystander effect.

TO THE EDITOR: In their Newsline commentary, Drs. Feinendegen and Pollycove call an important issue to the attention of readers of The Journal of Nuclear Medicine (1). In a discussion of the dual action of ionizing radiation, they posit a competition at low doses between the direct induction of radiation damage and the activation of damage control (adaptive response, hormesis), such that below 0.2 Gy the frequency of oncogenic transformation is lower than background and net radiation damage does not approximate the linear extrapolation model until 0.5 Gy (Fig. 10 of Feinendegen and Pollycove). In their text, Feinendegen and Pollycove (1) state that bystander cells (unirradiated neighbors of irradiated cells that are influenced by the latter) may respond similarly to those hit directly by radiation; indeed, there is evidence for this phenomenon (2). However, there is a robust literature, which the authors fail to mention, that suggests the bystander effect amplifies the consequences of irradiation rather than blunting them. Brenner et al. (3) propose a contrary model of the low-dose bystander effect. Their Figure 4 is the obverse of Figure 10 of Feinendegen and Pollycove (1). Accordingly, the induced rate of oncogenesis is greater (not less) than the linear extrapolation at doses below 0.4 Gy (40 cGy). In an attempt to explore the apparent competition between the adaptive response and the bystander effect, Sawant et al. have examined the results from irradiation of cells with -particle beams (4). When cell survival is the endpoint, a pronounced bystander effect, decreasing survival below that produced by direct irradiation alone, is reduced 50% on preirradiation with 2 cGy -photons as an adaptive stimulus. With radiation-induced transformation as the endpoint, an adaptive stimulus lessening a positive bystander effect could not be clearly demonstrated. All of this suggests that we are still ignorant of what really happens at low doses and that the case cannot be made facilely for responses either below or above the linear extrapolation.