Page 122 - 2014 Printable Abstract Book
P. 122
BRCA1 through regulating E2F1 expression in unstressed condition. Interestingly, in response to DSBs,
RNF126 regulates expression of E2F1 target genes involved in apoptosis, such as p73, by forming a
complex with E2F1. Moreover, RNF126 is important for Alt-NHEJ pathway, via promoting DSBs-induced
NBS1 phosphorylation and/or the complex formation of NBS1 and E2F1. Last, RNF126 deletion leads to
the increased sensitivity to ironizing radiation (IR) and PARP inhibitor. Overall, our results support a model
that RNF126 promotes HR, Alt-NHEJ and perhaps apoptosis by distinct mechanisms, but all of which are
related to E2F1. This study not only offers novel insights into our current understanding of RNF126
biological functions but also provides a new target for the cancer therapy. Key words: RNF126, E2F1,
BRCA1, NBS1, p73, Homologous Recombination (HR), Alternative non-homologous end joining (Alt-NHEJ).
(PS1-35) Dependence of rescue effect on relative abundance of bystander and irradiated cells.
2
1
1
R. K. K. Lam ; W. Han ; and K. N. Yu, Department of Physics and Materials Science, City University of Hong
1
Kong, Hong Kong, China and Center of Medical Physics and Technology, Hefei Institutes of Physical
Science, Chinese Academy of Sciences, Hefei, China
2
In the past two decades, accumulated evidence has demonstrated the Radiation-induced
bystander effects (RIBE) in both in vitro as well as in vivo studies, and extensive research has been carried
out to identify and characterize the bystander signals secreted by the irradiated cells. Recently, a closely
related phenomenon, coined as the “rescue effect”, has been revealed in both in vitro and in vivo studies,
where the bystander cells/organisms on receiving the bystander signals send feedback signals to the
irradiated cells/organisms to mitigate the biological effects on the irradiated cells/organisms.
In the present study, we studied the dependence of the rescue effect on the relative abundance of the
bystander cells, by employing the HeLa and NIH-3T3 cells under the confluence condition. We irradiated
2.5% or 75% of a cell population with alpha-particle doses of 5 or 20 cGy, respectively. The cells were fixed
at 12 h after irradiation and the 53bp1-positive cells were quantified through immunofluorescent staining.
Sham-irradiated and uniformly irradiated cells were used as control groups. For the case with 2.5% of the
cells irradiated by 5 cGy of alpha particles, the numbers of 53bp1-positive cells were found to be
significantly reduced by 1.5-fold and 2-fold, respectively, for HeLa and NIH-3T3 cells, as compared to the
uniformly irradiated cells, which demonstrated the rescue effect. When the dose was increased to 20 cGy,
the rescue effect was diminished, which showed that the rescue effect was dose dependent. For the case
with 75% of the cells irradiated by 5 cGy of alpha particles, the numbers of 53bp1-positive cells was found
to be significantly reduced by 1.2-fold in NIH-3T3 cells, but not significantly reduced in HeLa cells, as
compared to the uniformly irradiated cells. When the dose was increased to 20 cGy, the rescue effect
became insignificant although a small decrease in the number of 53bp1-positive cells was found in the
NIH-3T3 cells. In conclusion, our results showed stronger rescue effect for larger relative abundance of
bystander (i.e., smaller percentage of irradiated cells), but the relationship is also dose dependent and
cell-line dependent. These results provided insights for the mechanisms underlying the rescue effect, and
have far-reaching consequences on the radiotherapy procedures.
(PS1-36) Nanoscopic substructure of the protein foci at the DNA double strand breaks. Guanghua Du,
1
1
2
1
2
1
Doctor ; Ruqun Wu, Master ; Wenjing Liu, Master ; Qian Su ; Na Guo ; and Yujie Sun, Institute of Modern
2
Physics, Lanzhou, China and BIOPIC, Peking University, Beijing, China
1
120 | P a g e
RNF126 regulates expression of E2F1 target genes involved in apoptosis, such as p73, by forming a
complex with E2F1. Moreover, RNF126 is important for Alt-NHEJ pathway, via promoting DSBs-induced
NBS1 phosphorylation and/or the complex formation of NBS1 and E2F1. Last, RNF126 deletion leads to
the increased sensitivity to ironizing radiation (IR) and PARP inhibitor. Overall, our results support a model
that RNF126 promotes HR, Alt-NHEJ and perhaps apoptosis by distinct mechanisms, but all of which are
related to E2F1. This study not only offers novel insights into our current understanding of RNF126
biological functions but also provides a new target for the cancer therapy. Key words: RNF126, E2F1,
BRCA1, NBS1, p73, Homologous Recombination (HR), Alternative non-homologous end joining (Alt-NHEJ).
(PS1-35) Dependence of rescue effect on relative abundance of bystander and irradiated cells.
2
1
1
R. K. K. Lam ; W. Han ; and K. N. Yu, Department of Physics and Materials Science, City University of Hong
1
Kong, Hong Kong, China and Center of Medical Physics and Technology, Hefei Institutes of Physical
Science, Chinese Academy of Sciences, Hefei, China
2
In the past two decades, accumulated evidence has demonstrated the Radiation-induced
bystander effects (RIBE) in both in vitro as well as in vivo studies, and extensive research has been carried
out to identify and characterize the bystander signals secreted by the irradiated cells. Recently, a closely
related phenomenon, coined as the “rescue effect”, has been revealed in both in vitro and in vivo studies,
where the bystander cells/organisms on receiving the bystander signals send feedback signals to the
irradiated cells/organisms to mitigate the biological effects on the irradiated cells/organisms.
In the present study, we studied the dependence of the rescue effect on the relative abundance of the
bystander cells, by employing the HeLa and NIH-3T3 cells under the confluence condition. We irradiated
2.5% or 75% of a cell population with alpha-particle doses of 5 or 20 cGy, respectively. The cells were fixed
at 12 h after irradiation and the 53bp1-positive cells were quantified through immunofluorescent staining.
Sham-irradiated and uniformly irradiated cells were used as control groups. For the case with 2.5% of the
cells irradiated by 5 cGy of alpha particles, the numbers of 53bp1-positive cells were found to be
significantly reduced by 1.5-fold and 2-fold, respectively, for HeLa and NIH-3T3 cells, as compared to the
uniformly irradiated cells, which demonstrated the rescue effect. When the dose was increased to 20 cGy,
the rescue effect was diminished, which showed that the rescue effect was dose dependent. For the case
with 75% of the cells irradiated by 5 cGy of alpha particles, the numbers of 53bp1-positive cells was found
to be significantly reduced by 1.2-fold in NIH-3T3 cells, but not significantly reduced in HeLa cells, as
compared to the uniformly irradiated cells. When the dose was increased to 20 cGy, the rescue effect
became insignificant although a small decrease in the number of 53bp1-positive cells was found in the
NIH-3T3 cells. In conclusion, our results showed stronger rescue effect for larger relative abundance of
bystander (i.e., smaller percentage of irradiated cells), but the relationship is also dose dependent and
cell-line dependent. These results provided insights for the mechanisms underlying the rescue effect, and
have far-reaching consequences on the radiotherapy procedures.
(PS1-36) Nanoscopic substructure of the protein foci at the DNA double strand breaks. Guanghua Du,
1
1
2
1
2
1
Doctor ; Ruqun Wu, Master ; Wenjing Liu, Master ; Qian Su ; Na Guo ; and Yujie Sun, Institute of Modern
2
Physics, Lanzhou, China and BIOPIC, Peking University, Beijing, China
1
120 | P a g e
