Cellular communication and bystander effects: a critical review for modelling low-dose radiation action.

Available data suggesting the occurrence of "bystander effects" (i.e. damage induction in cells not traversed by radiation) were collected and critically evaluated, in view of the development of low-dose risk models. Although the underlying mechanisms are largely unknown, cellular communication seems to play a key role. In this context, the main features of cellular communication were summarised and a few representative studies on bystander effects were reported and discussed. Three main approaches were identified: (1) conventional irradiation of cell cultures with very low doses of light ions; (2) irradiation of single cells with microbeam probes; (3) treatment with irradiated conditioned medium (ICM), i.e. feeding of unexposed cells with medium taken from irradiated cultures. Indication of different types of bystander damage (e.g. cell killing, gene mutations and modifications in gene expression) has been found in each of the three cases. The interpretations proposed by the investigators were discussed and possible biases introduced by specific experimental conditions were outlined. New arguments and experiments were suggested, with the main purpose of obtaining quantitative information to be included in models of low-dose radiation action. Implications in interpreting low-dose data and modelling low-dose effects at cellular and supra-cellular level, including cancer induction, were analysed. Possible synergism with other low-dose specific phenomena such as adaptive response (AR) (i.e. low-dose induced resistance to subsequent irradiation) was discussed.