Role of TGF-beta1 and nitric oxide in the bystander response of irradiated glioma cells.

The radiation-induced bystander effect (RIBE) increases the probability of cellular response and therefore has important implications for cancer risk assessment following low-dose irradiation and for the likelihood of secondary cancers after radiotherapy. However, our knowledge of bystander signaling factors, especially those having long half-lives, is still limited. The present study found that, when a fraction of cells within a glioblastoma population were individually irradiated with helium ions from a particle microbeam, the yield of micronuclei (MN) in the nontargeted cells was increased, but these bystander MN were eliminated by treating the cells with either aminoguanidine (an inhibitor of inducible nitric oxide (NO) synthase) or anti-transforming growth factor beta1 (anti-TGF-beta1), indicating that NO and TGF-beta1 are involved in the RIBE. Intracellular NO was detected in the bystander cells, and additional TGF-beta1 was detected in the medium from irradiated T98G cells, but it was diminished by aminoguanidine. Consistent with this, an NO donor, diethylamine nitric oxide (DEANO), induced TGF-beta1 generation in T98G cells. Conversely, treatment of cells with recombinant TGF-beta1 could also induce NO and MN in T98G cells. Treatment of T98G cells with anti-TGF-beta1 inhibited the NO production when only 1% of cells were targeted, but not when 100% of cells were targeted. Our results indicate that, downstream of radiation-induced NO, TGF-beta1 can be released from targeted T98G cells and plays a key role as a signaling factor in the RIBE by further inducing free radicals and DNA damage in the nontargeted bystander cells.

Microbeam studies of the bystander response.

Microbeams have undergone a renaissance since their introduction and early use in the mid 60s. Recent advances in imaging, software and beam delivery have allowed rapid technological developments in microbeams for use in a range of experimental studies. The resurgence in the use of microbeams since the mid 90s has coincided with major changes in our understanding of how radiation interacts with cells. In particular, the evidence that bystander responses occur, where cells not directly irradiated can respond to irradiated neighbours, has brought about the evolution of new models of radiation response. Although these processes have been studied using a range of experimental approaches, microbeams offer a unique route by which bystander responses can be elucidated. Without exception, all of the microbeams currently active internationally have studied bystander responses in a range of cell and tissue models. Together these studies have considerably advanced our knowledge of bystander responses and the underpinning mechanisms. Much of this has come from charged particle microbeam studies, but increasingly, X-ray and electron microbeams are starting to contribute quantitative and mechanistic information on bystander effects. A recent development has been the move from studies with 2-D cell culture models to more complex 3-D systems where the possibilities of utilizing the unique characteristics of microbeams in terms of their spatial and temporal delivery will make a major impact.

Bystander behaviour as an influence on bullying in high schools

In response to evidence that bullying in schools persists in the presence of bystanders, this study sought to add to the existing knowledge about its reinforcing effects. The objectives of this research project were to investigate non-intervention in bullying incidents by students. Unique approaches of this research are the multi-dimensional investigation of the emotional, cognitive and behavioural factors from the bystander's perspective, within the context of a co-educational Catholic high school, in a sample of eighteen Year 8 students. In-depth and group interviews, participant observation and the input of a focus group of teachers formed the data collection. Previous findings that fear prevents bystanders from taking action, were extended by this study which revealed was that there are several sources of this fear. The study found reasons for students' fear included embarrassment at making a mistake, the importance of the teachers' responses, the need to assimilate into the new school culture, to be 'cool' and to avoid a negative, conforming self-image. Importantly, the existing focus on fear does not explain why students do not anonymously report bullying. This study found that students resisted taking responsibility for intervening, and unexpected findings included that students categorised victims, only caring enough to report bullying if the victim were a friend or sibling; and also that the thrill of watching bullying was a strong deterrent to bystander intervention. The study suggests, therefore, information based anti-bullying policies will be ineffective unless students are motivated to intervene. It is crucial that programmes now address the emotional deterrents of fear, excitement and apathy before considering educational approaches, and that future policies need to examine the culture of the school, including teachers' responses to bullying, which dictates the behavioural code for incoming Year 8 students.