Page 194 - 2014 Printable Abstract Book
P. 194
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(PS3-08) Transcriptional response in mouse to i.v. administered I is affected by time of day in a tissue-
3
3
1;2
1
specific manner. Britta Langen ; Nils Rudqvist ; Toshima Z. Parris, PhD ; Khalil Helou, Assoc. Prof. ; and
1
Eva Forssell-Aronsson, Prof. Dept of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer
Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg,
Sweden ; Dept of Applied Physics, Chalmers University of Technology, Gothenburg, Sweden ; and Dept of
2
1
Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of
3
Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
Objective: To demonstrate the effect of circadian rhythm on genome-wide transcriptional
responses to i.v. administered 131 I in mouse. Methods: Female BALB/c nude mice (n=4/group) were i.v.
injected with 90 kBq 131 I at 9:00 am, 12:00 pm, or 3:00 pm. For each time point, an individual control
(n=4/group) was mock-treated. Animals were killed 24 h after respective treatment and organs were
excised and flash-frozen. Total RNA was extracted from tissue samples of kidney cortex and medulla, liver,
lungs, spleen, and thyroid and analyzed on Illumina microarray beadchips. Significantly regulated
transcripts were identified with a fold change >1.5 and an adjusted P value <0.01. Literature-based
signature genes were used to evaluate the impact of ionizing radiation-associated and thyroid hormone-
associated responses. Tissue-specific absorbed dose was estimated using the MIRD formalism. Results:
The thyroid received 5.9 Gy over 24 h, while non-thyroid tissues received 0.75-2.2 mGy. The strongest
response was seen in the thyroid at 9 am with 1,015 differentially regulated transcripts. At 12 pm and 3
pm, 50 and 57 transcripts were regulated, respectively. Thirty transcripts responded at all-time points and
29 showed a distinct pattern with strong downregulation at 9 am and comparatively weak upregulation
at later times. The majority of these genes belong to the kallikrein family. In non-thyroid tissues, overall
responses were strongest in kidney medulla followed by liver and kidney cortex; each of these tissues
showed a pronounced maximum at 12 pm with 444, 184, and 105 regulated transcripts, respectively. In
contrast, 1-6 transcripts responded in the lungs and spleen at any time point, although absorbed dose in
non-thyroid tissues was similar. Responses of thyroid hormone-associated signature genes were on a
much higher level than responses of ionizing radiation-associated signature genes. Transcript response of
circadian rhythm core genes was negligible. Conclusion: The intensity and quality of transcriptional
131
responses to I after 24 h is sensitive to time of day from 9 am to 3 pm. Systemic effects originating from
the dominantly exposed thyroid are speculated to highly influence transcriptional responses in liver and
kidneys, but less in lungs and spleen. These are important considerations for biomarker discovery.
(PS3-09) Characterization of tumor spectrum, cognitive and ocular deficits arising in HZE ion irradiated
1
1
1
2
2
3
outbred mice. Jacob Raber ; John Belknap ; Ovidiu Iancue ; Norman Kleiman ; Eric Hall ; Andrew Ray ;
3
3
3
3
3
Christina Fallgren ; Debra Kamstock ; Elijah Edmondson ; Abbey Sadowski ; Adam King ; Catherine
3
1
3
Schmidt ; Michael Weil Oregon Health and Science University, Portland, OR ; Columbia University, New
2
York, NY ; and Colorado State University, Fort Collins, CO .
3
This project is designed to study the effects of HZE ion irradiation on a genetically heterogeneous
population. Eighteen hundred mice of the HS/Npt stock were either sham irradiated or irradiated with
137
HZE ions or Cs gamma rays. The mice are being monitored for tumorigenesis until they reach 800 days
192 | P a g e
(PS3-08) Transcriptional response in mouse to i.v. administered I is affected by time of day in a tissue-
3
3
1;2
1
specific manner. Britta Langen ; Nils Rudqvist ; Toshima Z. Parris, PhD ; Khalil Helou, Assoc. Prof. ; and
1
Eva Forssell-Aronsson, Prof. Dept of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer
Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg,
Sweden ; Dept of Applied Physics, Chalmers University of Technology, Gothenburg, Sweden ; and Dept of
2
1
Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of
3
Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
Objective: To demonstrate the effect of circadian rhythm on genome-wide transcriptional
responses to i.v. administered 131 I in mouse. Methods: Female BALB/c nude mice (n=4/group) were i.v.
injected with 90 kBq 131 I at 9:00 am, 12:00 pm, or 3:00 pm. For each time point, an individual control
(n=4/group) was mock-treated. Animals were killed 24 h after respective treatment and organs were
excised and flash-frozen. Total RNA was extracted from tissue samples of kidney cortex and medulla, liver,
lungs, spleen, and thyroid and analyzed on Illumina microarray beadchips. Significantly regulated
transcripts were identified with a fold change >1.5 and an adjusted P value <0.01. Literature-based
signature genes were used to evaluate the impact of ionizing radiation-associated and thyroid hormone-
associated responses. Tissue-specific absorbed dose was estimated using the MIRD formalism. Results:
The thyroid received 5.9 Gy over 24 h, while non-thyroid tissues received 0.75-2.2 mGy. The strongest
response was seen in the thyroid at 9 am with 1,015 differentially regulated transcripts. At 12 pm and 3
pm, 50 and 57 transcripts were regulated, respectively. Thirty transcripts responded at all-time points and
29 showed a distinct pattern with strong downregulation at 9 am and comparatively weak upregulation
at later times. The majority of these genes belong to the kallikrein family. In non-thyroid tissues, overall
responses were strongest in kidney medulla followed by liver and kidney cortex; each of these tissues
showed a pronounced maximum at 12 pm with 444, 184, and 105 regulated transcripts, respectively. In
contrast, 1-6 transcripts responded in the lungs and spleen at any time point, although absorbed dose in
non-thyroid tissues was similar. Responses of thyroid hormone-associated signature genes were on a
much higher level than responses of ionizing radiation-associated signature genes. Transcript response of
circadian rhythm core genes was negligible. Conclusion: The intensity and quality of transcriptional
131
responses to I after 24 h is sensitive to time of day from 9 am to 3 pm. Systemic effects originating from
the dominantly exposed thyroid are speculated to highly influence transcriptional responses in liver and
kidneys, but less in lungs and spleen. These are important considerations for biomarker discovery.
(PS3-09) Characterization of tumor spectrum, cognitive and ocular deficits arising in HZE ion irradiated
1
1
1
2
2
3
outbred mice. Jacob Raber ; John Belknap ; Ovidiu Iancue ; Norman Kleiman ; Eric Hall ; Andrew Ray ;
3
3
3
3
3
Christina Fallgren ; Debra Kamstock ; Elijah Edmondson ; Abbey Sadowski ; Adam King ; Catherine
3
1
3
Schmidt ; Michael Weil Oregon Health and Science University, Portland, OR ; Columbia University, New
2
York, NY ; and Colorado State University, Fort Collins, CO .
3
This project is designed to study the effects of HZE ion irradiation on a genetically heterogeneous
population. Eighteen hundred mice of the HS/Npt stock were either sham irradiated or irradiated with
137
HZE ions or Cs gamma rays. The mice are being monitored for tumorigenesis until they reach 800 days
192 | P a g e
