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Purpose: Risk assessment of radiation exposure during long-term space missions requires the knowledge of the relative biological effectiveness (RBE) of space radiation components. Few data on gene transcription activation by different heavy ions are available, suggesting a dependence on linear energy transfer. The transcription factor Nuclear Factor κB (NF-κB) can be involved in cancerogenesis. Therefore, NF-κB activation by accelerated heavy ions of different linear energy transfer (LET) was correlated to survival. Materials and methods: NF-κB-dependent gene induction after exposure to heavy ions was detected in stably transfected human embryonic kidney 293 cells (HEK-pNF-κB-d2EGFP/Neo cells carrying a neomycin resistance), using the destabilized Enhanced Green Fluorescent Protein (d2EGFP) as reporter. Results: Argon (LET 272 keV/μm) and neon ions (LET 91 keV/μm) had the highest potential to activate NF-κB, resulting in a RBE of 8.9 in comparison to 150 kV X-rays. The RBE for survival also reached its maximum in this LET range, with a maximal value of 2. Conclusions: NF-κB might be involved in modulating survival responses of cells hit by heavy ions in the LET range of 91-272 keV/μm and could therefore become a factor to be considered for risk assessment of radiation exposure during space travel. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate. Materials and methods: Non-tumour dose, Dnt, defined as the highest dose of radiation at which no statistically significant tumour increase was observed above the control level, was analysed as a function of dose-rate of radiation. Results: An inverse correlation was found between Dnt and dose-rate of the radiation. Dnt increased 20-fold with decreasing dose-rate from 1--10−−8 Gy/min for whole body irradiation with low linear energy transfer (LET) radiation. Partial body radiation also showed a dose-rate dependence with a 5- to 10-fold larger Dnt as dose rate decreased. The dose-rate effect was also found for high LET radiation but at 10-fold lower Dnt levels. Conclusions: The cancer risk of ionising radiation varies 1000-fold depending on the dose-rate of radiation and exposure conditions. This analysis explains the discrepancy of cancer risk between A-bomb survivors and radium dial painters. [ABSTRACT FROM AUTHOR]

Purpose: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. Materials and methods: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u[sup -1] iron particles, 400MeV u[sup -1] neon particles or γ-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or γ-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/Hoechst 33258 harlequin staining. Results: There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. Conclusion: The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided. [ABSTRACT FROM AUTHOR]