PARENT SESSION

Cell and Tissue Signaling

(PP278) Comparisons of effects of different charged particles in directly irradiated and bystander normal human fibroblasts.

Yang, Hongying^*,1, Anzenberg, Vered¹, Held, Kathryn¹, ¹ Department of Radiation Oncology, Boston, MA, USA

ABSTRACT- AG01522 normal human diploid fibroblast cells were irradiated with different charged particles including 1 GeV/amu iron ions (LET of 151 keV/m), 1 GeV/amu titanium ions (LET of 108 keV/m), 290 MeV/amu carbon ions (LET of 13 keV/m) and 1 GeV/amu protons (LET of 0.2 keV/m) at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory. Radiation-induced damage by different ions was evaluated in directly irradiated and bystander cells. In directly irradiated cells, the frequency of micronuclei formation varies with different ions. Compared to X-rays, the RBEs for producing 30% binucleate cells with micronuclei are about 1.5 for Fe and 1.1 for Ti. The RBEs for 10% cell survival are about 2.5 for Fe, 2.0 for Ti, 1.0 for C and 1.2 for protons. The four types of irradiation cause long lasting p21^Waf1 induction in directly irradiated cells. Forty hours after radiation, the percentages of cells with p21^Waf1 induction are similar in cells irradiated with Fe and protons, or in cells irradiated with C and Ti. This suggests that the RBEs for different radiation types are dependent on the specific endpoints, and different endpoints may have different correlations with LET. The transwell insert culture dish method was used to study the medium-mediated bystander effects. Surprisingly, an about 2-fold increase in frequency of micronuclei formation, which is similar to the effect we have reported previously with X-rays, is observed in bystander cells only after Fe irradiation. The cell survival of bystander cells is decreased by about 20% with Fe and C irradiation, but there is no significant change with Ti and proton irradiation. In addition, no p21^Waf1 induction is observed in bystander cells with the four types of irradiation, which is in contrast to the results with X-irradiation. These results suggest that the bystander effects of cell killing and micronuclei induction are independent of the LET of the radiation, even though the high LET radiation is more effective in causing damage in the directly irradiated cells. Also, it appears that p21^Waf1 induction in bystander cells and micronuclei formation or cell survival may occur by different pathways.

Key words: charged particles, AG01522 normal human fibroblasts, bystander effects, LET and RBE