Page 231 - 2014 Printable Abstract Book
P. 231
Further, these in vivo studies were supplemented with experiments using shRNA-mediated knockdown of
Egr1 in normal cell lines. Egr1 knockdown increased clonogenic survival in irradiated HT22 hippocampal
neuronal cells and IEC6 intestinal epithelial cells. The enhanced survival was associated with a reduction
of apoptosis in the Egr1 knockdown cells. In order to elucidate the molecular mechanism by which Egr1
knockdown diminishes apoptosis, we examined how Egr1 status can affect downstream transcriptional
targets involved in the mitochondrial pathway of apoptosis. In both Egr1 null mouse tissues and Egr1
knockdown cell lines, there was a decrease in radiation induction of Bim and Bax and an increase in Bcl-2
expression levels. These results suggest that Egr1 plays an important role in radiation-induced apoptosis
of hippocampal and intestinal tissues. Egr1 could be a potential molecular target to minimize the normal
tissue complications associated with radiotherapy.
(PS3-76) Comparative analysis of genomic profiles from human cell lines exposed to alpha particle
radiation. Vinita Chauhan; Matthew Howland; and Ruth Wilkins; Health Canada, Ottawa, Canada
Alpha particle radiation has become an increasing public health concern. The general population
is exposed though a variety of means, including ubiquitously from the environment (radon gas), when
using emerging radiotherapy modalities, accidently through occupational exposures and potentially from
a malicious terrorist threat. Previous work in our laboratory has identified genes responsive to alpha
particle radiation in five human-derived cell-lines which have included monocytes (THP-1), lung epithelial
cells (A549), keratinocytes (HEKn), lung fibroblasts (HFL-1) and isolated peripheral blood mononuclear
cells (PBMC) from healthy individuals. This report provides a meta-analysis of these previously published
studies. The results from this analysis indicate that at relatively small doses of radiation exposure (0.5-1.5
Gy), each of the cell-lines elicited a strong transcriptional response, modulating numerous transcripts. The
majority of the cell-lines expressed a unique sub-set of genes and several overlapping profiles were
observed for two or more of the cell-types. Thirty-six genes were common to all five cell-lines. Biological
processes associated with these genes included cell cycle/mitosis (FBXO5 ZWILCH CDKN1A DHFR MCM3
MCM7), telomere maintenance (ACD, HIST1H2BD, HIST1H4C) and DNA Replication (CDKN1A MCM3
MCM7). Hierarchical clustering of these transcripts separated cell-lines into two main groups whose
transcripts were characteristically expressed by specific tissue types. Overall, the results from this analysis
demonstrate that radiation exposure elicits cell-dependent differential genome-wide effects. However
despite distinctions, the end outcome is central to the process of DNA damage repair. By highlighting
common and differential responses between cell-lines at the transcriptional level with their associated
pathways/networks, an understanding of the cellular alpha particle radiation response has been
established along with the identification of potential biomarkers of exposure.
(PS3-77) 18F-FLT and 18F-5FU PET imaging and chemoradiotherapy for colorectal cancer. Thititip
Tippayamontri; Britgitte Guérin; Roger Lecomte; Benoit Paquette; and Leon Sanche, University of
Sherbrooke, Sherbrooke, Canada
Specific concomitant chemotherapy and radiotherapy has been shown to induce a synergistic
effect to increase the mean survival time of cancer patients compared to non-concomitant
229 | P a g e
Egr1 in normal cell lines. Egr1 knockdown increased clonogenic survival in irradiated HT22 hippocampal
neuronal cells and IEC6 intestinal epithelial cells. The enhanced survival was associated with a reduction
of apoptosis in the Egr1 knockdown cells. In order to elucidate the molecular mechanism by which Egr1
knockdown diminishes apoptosis, we examined how Egr1 status can affect downstream transcriptional
targets involved in the mitochondrial pathway of apoptosis. In both Egr1 null mouse tissues and Egr1
knockdown cell lines, there was a decrease in radiation induction of Bim and Bax and an increase in Bcl-2
expression levels. These results suggest that Egr1 plays an important role in radiation-induced apoptosis
of hippocampal and intestinal tissues. Egr1 could be a potential molecular target to minimize the normal
tissue complications associated with radiotherapy.
(PS3-76) Comparative analysis of genomic profiles from human cell lines exposed to alpha particle
radiation. Vinita Chauhan; Matthew Howland; and Ruth Wilkins; Health Canada, Ottawa, Canada
Alpha particle radiation has become an increasing public health concern. The general population
is exposed though a variety of means, including ubiquitously from the environment (radon gas), when
using emerging radiotherapy modalities, accidently through occupational exposures and potentially from
a malicious terrorist threat. Previous work in our laboratory has identified genes responsive to alpha
particle radiation in five human-derived cell-lines which have included monocytes (THP-1), lung epithelial
cells (A549), keratinocytes (HEKn), lung fibroblasts (HFL-1) and isolated peripheral blood mononuclear
cells (PBMC) from healthy individuals. This report provides a meta-analysis of these previously published
studies. The results from this analysis indicate that at relatively small doses of radiation exposure (0.5-1.5
Gy), each of the cell-lines elicited a strong transcriptional response, modulating numerous transcripts. The
majority of the cell-lines expressed a unique sub-set of genes and several overlapping profiles were
observed for two or more of the cell-types. Thirty-six genes were common to all five cell-lines. Biological
processes associated with these genes included cell cycle/mitosis (FBXO5 ZWILCH CDKN1A DHFR MCM3
MCM7), telomere maintenance (ACD, HIST1H2BD, HIST1H4C) and DNA Replication (CDKN1A MCM3
MCM7). Hierarchical clustering of these transcripts separated cell-lines into two main groups whose
transcripts were characteristically expressed by specific tissue types. Overall, the results from this analysis
demonstrate that radiation exposure elicits cell-dependent differential genome-wide effects. However
despite distinctions, the end outcome is central to the process of DNA damage repair. By highlighting
common and differential responses between cell-lines at the transcriptional level with their associated
pathways/networks, an understanding of the cellular alpha particle radiation response has been
established along with the identification of potential biomarkers of exposure.
(PS3-77) 18F-FLT and 18F-5FU PET imaging and chemoradiotherapy for colorectal cancer. Thititip
Tippayamontri; Britgitte Guérin; Roger Lecomte; Benoit Paquette; and Leon Sanche, University of
Sherbrooke, Sherbrooke, Canada
Specific concomitant chemotherapy and radiotherapy has been shown to induce a synergistic
effect to increase the mean survival time of cancer patients compared to non-concomitant
229 | P a g e
