The bystander effect: recent developments and implications for understanding the dose response

The bystander effect refers to the biological response of a cell resulting from an event in an adjacent or nearby cell. Such effects depend on intercellular communication and amplify the consequences of the original event. These responses are of particular interest in the assessment of ionizing radiation risk because at public or occupational exposure levels not every cell receives a radiation track. Current radiation protection regulations and practices are based on the assumption of a linear increase in risk with dose, including low doses where not all cells are hit. Mechanisms that amplify biological effects are inconsistent with these assumptions. Evidence suggests that there are two different bystander effects in mammalian cells. In one type, a radiation track in one cell leads to damaging, mutagenic, and sometimes lethal events in adjacent, unhit cells. In the other type, a radiation track in one cell leads to an adaptive response in bystander cells, increasing resistance to spontaneous or radiation-induced events. This paper describes some of the data for radiation-induced bystander effects in vitro and correlates that data with in vitro and in vivo observations of risk at low doses. The data suggest that protective effects, including beneficial bystander effects, outweigh detrimental effects at doses below about 100 mGy, but that the reverse is true above this threshold.