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Purpose: To further evaluate the use of microbeam irradiation (MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue. Methods: Adult rats were irradiated with 35 or 350 Gy at the European Synchotron Research Facility (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam delivered to the right brain hemisphere only. The proteome of the frontal lobes were then analyzed using two-dimensional electrophoresis (2-DE) and mass spectrometry. Results: HI resulted in proteomic responses indicative of tumourigenesis; increased albumin, aconitase and triosphosphate isomerase (TPI), and decreased dihydrolipoyldehydrogenase (DLD). The MBI bystander effect proteomic changes were indicative of reactive oxygen species mediated apoptosis; reduced TPI, prohibitin and tubulin and increased glial fibrillary acidic protein (GFAP). These potentially anti-tumourigenic apoptotic proteomic changes are also associated with neurodegeneration. However the bystander effect also increased heat shock protein (HSP) 71 turnover. HSP 71 is known to protect against all of the neurological disorders characterized by the bystander effect proteome changes. Conclusions: These results indicate that the collective interaction of these MBI-induced bystander effect proteins and their mediation by HSP 71, may confer a protective effect which now warrants additional experimental attention. [ABSTRACT FROM AUTHOR]

Purpose: A number of contradictory studies have reported a role or not for p53 (protein 53) in the production of radiation-induced bystander effects. Most of these studies looked at a range of cell lines with normal or compromised p53 function. Methods: In this study, Human Colon Tumour line 116 (HCT 116) cells with confirmed wild type p53 function and a corresponding p53 null HCT 116 line were used to test for bystander signal production and response to bystander signals in a mix/match protocol using the medium transfer technique. Results: The results showed that both the null cells and the wild type cells produced bystander signals. However, only the p53 wild type cells responded to signals from either cell line. The Human Papilloma Virus transfected keratinocyte line G (HPV-G) reporter cell line used routinely in our laboratory was used to confirm that the null cells were producing signals. Conclusions: We conclude that in this system the p53 pathway is involved in response of cells to bystander signals but that signals can be produced by cells which do not have functional p53. If these results apply in vivo, they could be important in radiotherapy where tumours may have compromised p53 function but surrounding (and distant) normal tissue may have wild type functional p53. [ABSTRACT FROM AUTHOR]

Two almost completely exclusive fields in radiobiology deal with splitting doses of radiation and comparing the effect to a similar total dose given in one exposure. In radiotherapy, dose "fractionation" is used to "spare" normal tissue and in the low dose field, the adaptive response is well documented as a phenomenon where a small "priming" dose administered before the larger "challenge " dose reduces the effect of the large dose. There have been very few studies where these fields overlap, thus it is not possible to ascertain whether common or distinct mechanisms underlie both phenomena but this is certainly an interesting question and relevant to our understanding of high and low dose radiobiology. This paper presents data for three human cell lines with varying p53 status and radiation responses, treated at a range of times between first and second dose and for 3 different first doses (0.1, 0.5 and 2Gy). The data show that time between doses is critical. Protective (adaptive) effects were seen in each cell line but most prominently in the malignant HT 29 cell line. Surprisingly none of the cell lines showed pronounced split dose recovery. This suggests different mechanisms may underlie the two phenomena. [ABSTRACT FROM AUTHOR]

The term radiation-induced bystander effects describes a situation where cells that have not been directly exposed to ionizing radiation behave as though they have been exposed: they die or they show chromosomal instability and other abnormalities. The bystander cells might be immediately adjacent or might be some distance away from the exposed cell. Although the nature of the communication system that is involved in producing these responses is not yet known, there is strong evidence for a chemical signalling process that transmits information from the irradiated cell to neighbouring cells. The bystander effect has several important implications for radiation protection, radiotherapy and diagnostic radiology. [ABSTRACT FROM AUTHOR]