Page 366 - 2014 Printable Abstract Book
P. 366
expression profiling. Flow cytometry revealed that IR increased the percentage of endothelial cells
(relative to the whole cell population) in both the hippocampus and the cerebellum, indicating that other
cell types were more susceptible to IR-induced cell death. However, IR suppressed proliferation of
endothelial cells, as judged by a decreased percentage of cells in S phase and an increased percentage in
G0/G1 phase of the cell cycle 6 hours after IR. Genes involved in endothelial cell-specific apoptosis (e.g.
ASMase) were not induced at any time point investigated. Inflammation-related genes, on the other hand,
were strongly induced, such as CCL2, CCL11 and IL-6. We conclude that endothelial cells do not undergo
apoptotic cell death to the same extent as other cell types in the hippocampus and the cerebellum after
IR, but that they display reduced cell proliferation. In addition, we demonstrate that endothelial cells play
an active, hitherto unknown, role, in the in the inflammatory response after IR.
(PS7-24) Association of stable and unstable chromosome translocations with low dose occupational
1
2
radiation exposures in US radiologic technologists. Mark P. Little, D.Phil. ; Deukwoo Kwon, PhD ;
1
1
1
3
Kazataka Doi, PhD ; Steven L. Simon, PhD ; Dale L. Preston, PhD ; Michele M. Doody ; Diane M. Kampa,
5
4
1
6
1
BSB. ; Parveen Bhatti, PhD ; James D. Tucker, PhD ; Martha S. Linet, MD ; and Alice J. Sigurdson, PhD ;
1
2
National Cancer Institute, Bethesda, MD ; University of Miami, Miami, FL ; Hirosoft International, Eureka,
5
3
4
CA ; University of Minnesota, Minneapolis, MN ; Fred Hutchinson Cancer Research Center, Seattle, WA ;
and Wayne State University, Detroit, MI
6
Chromosome translocations are a well-recognized biological marker of radiation exposure and
cancer risk. However, there is uncertainty about the lowest dose at which excess translocations can be
detected. Dosimetric uncertainties can substantially alter the shape of dose-response relationships;
although regression-calibration methods have been used in some datasets, these have not been applied
in radio-occupational studies, where there are also complex patterns of shared and unshared errors that
these methods do not account for. We evaluated the relationship between estimated occupational
ionizing radiation doses and stable and unstable chromosome translocation rates using fluorescent in situ
hybridization in 238 US radiologic technologists selected from a large cohort. Dosimetric uncertainties
were evaluated using regression-calibration, Bayesian, and Monte-Carlo maximum-likelihood methods,
taking account of shared and unshared error, and adjusted for overdispersion.
For stable chromosome translocations there was a significant dose response for estimated occupational
radiation exposure, adjusted for personal diagnostic radiation, age, sex, and study group (5.7 trans-
locations per 100 whole-genome cell equivalents per Gy, 95% CI 0.2, 11.3, p=0.0440). A significant
increasing trend with dose continued to be observed for individuals with estimated doses <100 mGy. The
three methods of analysis to adjust for dose uncertainty gave similar results. Analysis of unstable
aberrations suggested borderline significant increasing trends in relation to PDM dose for fragments
(p=0.0870) and all unstable aberrations (p=0.0992). The slopes of the trends with dose were markedly less
than for stable aberrations, e.g., for all unstable aberrations, the dose-response was 1.2 (95% CI -0.2, 2.7)
x 10-2 translocations Gy-1. In summary, stable chromosome translocation dose-response slopes were
detectable down to <100 mGy, and were compatible with those observed in other radiation-exposed
populations. There are weaker and borderline significant (0.1 > p > 0.05) indications of dose response also
for certain types of unstable aberrations. However, there are substantial uncertainties in both
occupational and other (diagnostic medical) doses that may be imperfectly taken into account in our
analysis.
364 | P a g e
(relative to the whole cell population) in both the hippocampus and the cerebellum, indicating that other
cell types were more susceptible to IR-induced cell death. However, IR suppressed proliferation of
endothelial cells, as judged by a decreased percentage of cells in S phase and an increased percentage in
G0/G1 phase of the cell cycle 6 hours after IR. Genes involved in endothelial cell-specific apoptosis (e.g.
ASMase) were not induced at any time point investigated. Inflammation-related genes, on the other hand,
were strongly induced, such as CCL2, CCL11 and IL-6. We conclude that endothelial cells do not undergo
apoptotic cell death to the same extent as other cell types in the hippocampus and the cerebellum after
IR, but that they display reduced cell proliferation. In addition, we demonstrate that endothelial cells play
an active, hitherto unknown, role, in the in the inflammatory response after IR.
(PS7-24) Association of stable and unstable chromosome translocations with low dose occupational
1
2
radiation exposures in US radiologic technologists. Mark P. Little, D.Phil. ; Deukwoo Kwon, PhD ;
1
1
1
3
Kazataka Doi, PhD ; Steven L. Simon, PhD ; Dale L. Preston, PhD ; Michele M. Doody ; Diane M. Kampa,
5
4
1
6
1
BSB. ; Parveen Bhatti, PhD ; James D. Tucker, PhD ; Martha S. Linet, MD ; and Alice J. Sigurdson, PhD ;
1
2
National Cancer Institute, Bethesda, MD ; University of Miami, Miami, FL ; Hirosoft International, Eureka,
5
3
4
CA ; University of Minnesota, Minneapolis, MN ; Fred Hutchinson Cancer Research Center, Seattle, WA ;
and Wayne State University, Detroit, MI
6
Chromosome translocations are a well-recognized biological marker of radiation exposure and
cancer risk. However, there is uncertainty about the lowest dose at which excess translocations can be
detected. Dosimetric uncertainties can substantially alter the shape of dose-response relationships;
although regression-calibration methods have been used in some datasets, these have not been applied
in radio-occupational studies, where there are also complex patterns of shared and unshared errors that
these methods do not account for. We evaluated the relationship between estimated occupational
ionizing radiation doses and stable and unstable chromosome translocation rates using fluorescent in situ
hybridization in 238 US radiologic technologists selected from a large cohort. Dosimetric uncertainties
were evaluated using regression-calibration, Bayesian, and Monte-Carlo maximum-likelihood methods,
taking account of shared and unshared error, and adjusted for overdispersion.
For stable chromosome translocations there was a significant dose response for estimated occupational
radiation exposure, adjusted for personal diagnostic radiation, age, sex, and study group (5.7 trans-
locations per 100 whole-genome cell equivalents per Gy, 95% CI 0.2, 11.3, p=0.0440). A significant
increasing trend with dose continued to be observed for individuals with estimated doses <100 mGy. The
three methods of analysis to adjust for dose uncertainty gave similar results. Analysis of unstable
aberrations suggested borderline significant increasing trends in relation to PDM dose for fragments
(p=0.0870) and all unstable aberrations (p=0.0992). The slopes of the trends with dose were markedly less
than for stable aberrations, e.g., for all unstable aberrations, the dose-response was 1.2 (95% CI -0.2, 2.7)
x 10-2 translocations Gy-1. In summary, stable chromosome translocation dose-response slopes were
detectable down to <100 mGy, and were compatible with those observed in other radiation-exposed
populations. There are weaker and borderline significant (0.1 > p > 0.05) indications of dose response also
for certain types of unstable aberrations. However, there are substantial uncertainties in both
occupational and other (diagnostic medical) doses that may be imperfectly taken into account in our
analysis.
364 | P a g e
