Bystander effect, radiation-induced

Muroya Y, Plante I, Azzam El, Meesimgnoen J, Katsumura Y, Jay-Gerin JP. (2006) High-LET ion radiolysis of water Visualization of the formation and evolution of ion tracks and relevance to the radiation-induced bystander effect. Radiat Res 165 485 91. 

Radiation-induced genomic instability and bystander effects are now well-established consequences of exposure of living cells to ionizing radiation. Cells not directly traversed by radiation may still exhibit radiation effects. This phenomenon, known as bystander effect, has become a major activity in radiation biology and in some cases has challenged the conventional wisdom. An example is the currently accepted models used for low-dose extrapolation of radiation risks. The currently used models assume that cells in an irradiated population respond individually rather than collectively. If bystander effects have implications for health risks estimates from exposure to ionizing radiation, then the question of whether this is a general phenomenon or solely a characteristic of a particular type of cell and the radiation under test becomes an important issue. 

It is seen from this table that, at the LD50 level, the nucleus has received about the same dose, irrespective of whether X-rays, 3H-dThd or 125I-concanavalin are used as the source of ionizing radiation, while the membrane has received an immense dose with 125I-concanavalin and very little with 3H-dThd. As expected, the cytoplasm lies in between these two extremes. Yet, irradiation of the cytoplasm (single-ion-beam experiments) is not without an effect. It may cause mutations (Wu et al. 1999) and the formation of products that induce apoptosis in nearby (unirradiated) cells (bystander effect Shao et al. 2004). 

Ward, J.F. The radiation-induced lesions which trigger the bystander effect. Mutat. Res. Fundam. Mol. Mech. Mutagen 2002, 499, 151. 

Greene-Schloesser, D., Robbins, M.E., 2012. Radiation-induced cognitive impair-ment-from bench to bedside. Neuro Oncol. 14 (Suppl. 4), iv37-iv44. Hamada, N., Maeda, M., Otsuka, K., et al., 2011. Signaling pathways underpinning the manifestations of ionizing radiation-induced bystander effects. Curr. Mol. Pharmacol. 2, 79-95. 

Mothersill, C., Seymour, C.B., 1998. Cell-cell contact during y-irradiation is not required to induce a bystander effect in normal human keratinocytes evidence for release during irradiation of a signal controlling survival into the medium. Radiat. Res. 149, 256-262. 

During the last decade it has become increasingly evident that the cytotoxic effects of radiotherapy on tumors are not only the result of the DNA damage inflicted to the tumor cells. Radiation can induce the release of several factors, with direct or indirect cytotoxic capacity, not only from tumor cells but also from different bystander cells that can trigger death of tumor cells. 

One early study of the effect of in vivo radiation could not verify any increase of iNOS in the brain after radiation although NO-inducing cytokines such as TNF-a and IL-ip were up-regulated (Hong et al. 1995). However, in vitro induction of NO in tumor cells by IFN-y treatment as well as by irradiation itself was shown to substantially increase the radiosensitivity of not only these cells but also bystander cells (Janssens et al. 1998 Matsumoto et al. 2000). 

---