Radiation bystander effects

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. 

Nagasawa, H., Little, J.B., 1999. Unexpected sensitivity to the induction of mutations by very low doses of a-particle radiation evidence for a bystander effect. Radiat. Res. 152, 552-557. 

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. 

The bystander effect has been observed for a variety of biological end points such as cell survival [158 159], mutation [160-162], sister chromatid exchanges [163], cell transformation [164,165], micronucleated and apoptosis [166], gene expression [167], and radiation genomic instability [168-170]. 

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). 

Single charged-particle beam irradiation of single cells has been developed to study various aspects of radiation biology such as the bystander effect. This subject exceeds the scope of this book, and only some reference to this technique is made here (Folkard et al. 1997a,b). 

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

The relative contribution of both of these pathways depends on the particular tis sue under consideration. The information exchange between cells plays a key role for the so-called bystander effect , which describes the fact that even cells not di rectly damaged by radiation can be affected indirectly by signals received from di rectly damaged cells [12-14]. 

The above-mentioned bystander effects are expected to be of importance for understanding the response of tissues to radiation Injury, because cells in a tissue are usually connected by complex communication networks. In fact there are first indications that bystander effects cannot only be detected in in vitro systems, but also in in vivo-like systems such as, e.g., tissue explants [101]. Since bystander effects play a role at low doses and low fluences, they might be in particular relevant for studies of mutation and transformation related to radiation protection. For applications of ion beams in tumor therapy, doses and thus fluences are usually comparably high, so that the fraction of unhit cells is small. 

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. 

Shao, C., Aoki, M., and Furusawa, Y. (2004). Bystander effect in lymphoma cells vicinal to irradiated neoplastic epithelial cells nitric oxide is involved. J. Radiat. Res. (Tokyo) 45, 97-103. 

Prise, K.M., Belyakov, O.V., Newman, H.C, et al., 2002. Non-targeted effects of radiation bystander responses in cell and tissue models. Radiat Prot... 

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). 

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