Page 335 - 2014 Printable Abstract Book
P. 335
(PS6-18) Demographic study using the cytokinesis-block micronucleus (CBMN) assay to assess the need
for separate calibration curves among different demographic groups in determining past acute
1
1
1
1
radiation exposure. Richard J. Kowalski, PhD ; Johnny Ho ; Matthew Snyder ; Monta Whitney ; Nariman
3
3
3
3
2
Panahian, MD ; David Brenner, PhD ; Guy Garty, PhD ; Adayabalam Balajee, PhD ; Helen Turner, PhD ; Jay
5
6
4
3
1
Perrier ; Courtney Ashton ; Evan Hempel ; Derek Muse, MD ; and Douglas Henderson, PhD ; Northrop
1
3
2
Grumman Corporation, Elkridge, MD ; Aerotek, Inc., Elkridge, MD ; Columbia University, New York, NY ;
4
5
KAI-Research, Inc., Rockville, MD ; KAI-Research, Rockville, MD ; and Jean Brown Research, Salt Lake City,
UT
6
The cytokinesis-block micronucleus (CBMN) assay has been proven as a reliable and quantitative
assay in determining past acute radiation exposure levels. A demographic study using ex-vivo irradiated
blood samples from human adults ranging from ages 21 to 79 was designed and executed to assess
whether separate calibration dose response curves would be required for different demographic groups
in the population. In addition to age and gender, a donor’s smoking, Type II diabetes, alcohol and caffeine
consumption status was also incorporated into the study design. A total of 242 donors were enrolled in
the study. Peripheral blood samples (~5mL) were collected from healthy volunteers at Jean Brown
Research after informed consent was obtained. Blood samples were shipped inside a temperature-
controlled container to the Center for Radiological Research at Columbia University for CBMN analysis.
Each blood sample was divided into 6 aliquots, with each aliquot receiving one of the following radiation
137
doses (0, 1.5, 2.5, 5, 7.5, 10Gy) from a Cesium source. Lymphocytes were isolated, cultured, cytokinesis-
blocked, and fixed/stained. Imaging was carried out using an Olympus BX43 microscope with automated
scoring of micronuclei, mononucleates and binucleates. Raw data from the CBMN assay was uploaded to
KAI-Research, Inc. for archival and statistical analysis. Early statistical analysis confirmed definitive
correlation between radiation dose and CBMN assay signal intensity. The preliminary analysis showed
that there was no statistical difference between the different demographic groups with respect to number
of micronuclei generated at each dose level. This indicates the CBMN assay is a robust, independent
measure of radiation dose; eliminating the need for multiple calibration curves. This project has been
funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development
Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary,
Department of Health and Human Services, under Contract No. HHSO100201000002C.
(PS6-19) The effects of low-dose rate external ionizing radiation on urinary metabolomic responses in
2
3
1
3
vivo. Maryam Goudarzi ; Tytus D. Mak, MS ; Congju Chen, MS ; Lubomir B. Smilenov, PhD ; David J.
1;2
3
Brenner, PhD ; and Albert J. Fornace Jr., MD ; Biochemistry and Molecular and Cellular Biology,
1
Georgetown University, Washington DC, DC ; Lombardi Comprehensive Cancer Center, Georgetown
2
University, Washington DC, DC ; and Center for High-Throughput Minimally-Invasive Radiation
3
Biodosimetry, Columbia University, New York, NY
Our previous studies have been focused on [[Unsupported Character - Symbol Font γ]]-irradiation
at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at
relatively low dose rates (LDR). Based on the previously observed gene expression differences in the
biologic effects and responses to LDR compared to HDR, we set out to study the effects of LDR exposure
at the metabolomic level in urine. In accordance with our previous studies we chose C57/Bl6 mice as our
model and collected 24-hour urine samples from them after exposure to 1, 2, and 4 Gy HDR (1 Gy/min)
333 | P a g e
for separate calibration curves among different demographic groups in determining past acute
1
1
1
1
radiation exposure. Richard J. Kowalski, PhD ; Johnny Ho ; Matthew Snyder ; Monta Whitney ; Nariman
3
3
3
3
2
Panahian, MD ; David Brenner, PhD ; Guy Garty, PhD ; Adayabalam Balajee, PhD ; Helen Turner, PhD ; Jay
5
6
4
3
1
Perrier ; Courtney Ashton ; Evan Hempel ; Derek Muse, MD ; and Douglas Henderson, PhD ; Northrop
1
3
2
Grumman Corporation, Elkridge, MD ; Aerotek, Inc., Elkridge, MD ; Columbia University, New York, NY ;
4
5
KAI-Research, Inc., Rockville, MD ; KAI-Research, Rockville, MD ; and Jean Brown Research, Salt Lake City,
UT
6
The cytokinesis-block micronucleus (CBMN) assay has been proven as a reliable and quantitative
assay in determining past acute radiation exposure levels. A demographic study using ex-vivo irradiated
blood samples from human adults ranging from ages 21 to 79 was designed and executed to assess
whether separate calibration dose response curves would be required for different demographic groups
in the population. In addition to age and gender, a donor’s smoking, Type II diabetes, alcohol and caffeine
consumption status was also incorporated into the study design. A total of 242 donors were enrolled in
the study. Peripheral blood samples (~5mL) were collected from healthy volunteers at Jean Brown
Research after informed consent was obtained. Blood samples were shipped inside a temperature-
controlled container to the Center for Radiological Research at Columbia University for CBMN analysis.
Each blood sample was divided into 6 aliquots, with each aliquot receiving one of the following radiation
137
doses (0, 1.5, 2.5, 5, 7.5, 10Gy) from a Cesium source. Lymphocytes were isolated, cultured, cytokinesis-
blocked, and fixed/stained. Imaging was carried out using an Olympus BX43 microscope with automated
scoring of micronuclei, mononucleates and binucleates. Raw data from the CBMN assay was uploaded to
KAI-Research, Inc. for archival and statistical analysis. Early statistical analysis confirmed definitive
correlation between radiation dose and CBMN assay signal intensity. The preliminary analysis showed
that there was no statistical difference between the different demographic groups with respect to number
of micronuclei generated at each dose level. This indicates the CBMN assay is a robust, independent
measure of radiation dose; eliminating the need for multiple calibration curves. This project has been
funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development
Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary,
Department of Health and Human Services, under Contract No. HHSO100201000002C.
(PS6-19) The effects of low-dose rate external ionizing radiation on urinary metabolomic responses in
2
3
1
3
vivo. Maryam Goudarzi ; Tytus D. Mak, MS ; Congju Chen, MS ; Lubomir B. Smilenov, PhD ; David J.
1;2
3
Brenner, PhD ; and Albert J. Fornace Jr., MD ; Biochemistry and Molecular and Cellular Biology,
1
Georgetown University, Washington DC, DC ; Lombardi Comprehensive Cancer Center, Georgetown
2
University, Washington DC, DC ; and Center for High-Throughput Minimally-Invasive Radiation
3
Biodosimetry, Columbia University, New York, NY
Our previous studies have been focused on [[Unsupported Character - Symbol Font γ]]-irradiation
at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at
relatively low dose rates (LDR). Based on the previously observed gene expression differences in the
biologic effects and responses to LDR compared to HDR, we set out to study the effects of LDR exposure
at the metabolomic level in urine. In accordance with our previous studies we chose C57/Bl6 mice as our
model and collected 24-hour urine samples from them after exposure to 1, 2, and 4 Gy HDR (1 Gy/min)
333 | P a g e
