Summary of Study ST001791
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001137. The data can be accessed directly via it's Project DOI: 10.21228/M8R102 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST001791 |
Study Title | Effect of external low-dose rate radiation on mouse biofluid metabolomic signatures (part II) |
Study Summary | An important component of ionizing radiation (IR) exposure after a radiological incident may include low-dose rate (LDR) exposures either externally or internally, such as from 137Cs deposition. LDR exposures can have different effects compared to acute high-dose rate exposures from a health and biodosimetry perspective. In this study, a novel irradiation system, VAriable Dose-rate External 137Cs irradiatoR (VADER), was used to expose male and female mice to a variable LDR over a 30-day time span to cumulative doses of 1 (only in males), 2, 2.8, 4.1, 8.8 (only in males), or 9.7 Gy to simulate fall-out type exposures. Urine and serum from mice exposed to an acute dose (~0.8 Gy/min) of x-rays were collected in parallel. Radiation markers were identified by global mass spectrometry based metabolomics and the machine learning algorithm Random Forests. |
Institute | Georgetown University |
Last Name | Pannkuk |
First Name | Evan |
Address | 3970 Reservoir Rd, NW New Research Building E504 |
elp44@georgetown.edu | |
Phone | 2026875650 |
Submit Date | 2021-05-11 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Waters) |
Analysis Type Detail | LC-MS |
Release Date | 2021-12-15 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR001137 |
Project DOI: | doi: 10.21228/M8R102 |
Project Title: | Effect of external low-dose rate (LDR) radiation on mouse biofluid metabolomic |
Project Summary: | An important component of ionizing radiation (IR) exposure after a radiological incident may include low-dose rate (LDR) exposures either externally or internally, such as from 137Cs deposition. LDR exposures can have different effects compared to acute high-dose rate exposures from a health and biodosimetry perspective. In this study, a novel irradiation system, VAriable Dose-rate External 137Cs irradiatoR (VADER), was used to expose male and female mice to a variable LDR over a 30-day time span to cumulative doses of 1 (only in males), 2, 2.8, 4.1, 8.8 (only in males), or 9.7 Gy to simulate fall-out type exposures. Urine and serum from mice exposed to an acute dose (~0.8 Gy/min) of x-rays were collected in parallel. Radiation markers were identified by global mass spectrometry based metabolomics and the machine learning algorithm Random Forests. |
Institute: | Georgetown University |
Last Name: | Pannkuk |
First Name: | Evan |
Address: | 3970 Reservoir Rd, NW New Research Building E504 |
Email: | elp44@georgetown.edu |
Phone: | 2026875650 |
Subject:
Subject ID: | SU001868 |
Subject Type: | Mammal |
Subject Species: | Mus musculus |
Taxonomy ID: | 10090 |
Genotype Strain: | C57BL/6 |
Gender: | Female |
Animal Animal Supplier: | Charles River |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
mb_sample_id | local_sample_id | Factor | Factor |
---|---|---|---|
SA166757 | 115 | A | post |
SA166758 | 63 | Control | post |
SA166759 | 61 | Control | post |
SA166760 | 159 | Control | post |
SA166761 | 66 | Control | post |
SA166762 | 107 | Control | post |
SA166763 | 52 | Control | post |
SA166764 | 116 | Control | post |
SA166765 | 165 | Control | post |
SA166766 | 48 | Control | post |
SA166767 | 101 | Control | post |
SA166768 | 112 | Control | post |
SA166769 | 70 | Control | post |
SA166770 | 151 | Control | post |
SA166771 | 216 | Control | post |
SA166772 | 150 | Control | post |
SA166773 | 88 | Control | post |
SA166774 | 144 | Control | post |
SA166775 | 80 | Control | post |
SA166776 | 143 | Control | post |
SA166777 | 138 | Control | post |
SA166778 | 74 | Control | post |
SA166779 | 222 | Control | post |
SA166780 | 193 | Control | post |
SA166781 | 192 | Control | post |
SA166782 | 231 | Control | post |
SA166783 | 25 | Control | post |
SA166784 | 24 | Control | post |
SA166785 | 185 | Control | post |
SA166786 | 40 | Control | post |
SA166787 | 28 | Control | post |
SA166788 | 22 | Control | post |
SA166789 | 17 | Control | post |
SA166790 | 241 | Control | post |
SA166791 | 10 | Control | post |
SA166792 | 184 | Control | post |
SA166793 | 177 | Control | post |
SA166794 | 238 | Control | post |
SA166795 | 170 | Control | post |
SA166796 | 27 | Control | post |
SA166797 | 120 | Control | post |
SA166798 | 125 | Control | post |
SA166799 | 207 | Control | post |
SA166800 | 38 | Control | post |
SA166801 | 209 | Control | post |
SA166802 | 130 | Control | pre |
SA166803 | 95 | Control | pre |
SA166804 | 139 | Control | pre |
SA166805 | 94 | Control | pre |
SA166806 | 182 | Control | pre |
SA166807 | 113 | Control | pre |
SA166808 | 91 | Control | pre |
SA166809 | 202 | Control | pre |
SA166810 | 141 | Control | pre |
SA166811 | 103 | Control | pre |
SA166812 | 105 | Control | pre |
SA166813 | 126 | Control | pre |
SA166814 | 196 | Control | pre |
SA166815 | 140 | Control | pre |
SA166816 | 104 | Control | pre |
SA166817 | 9 | Control | pre |
SA166818 | 137 | Control | pre |
SA166819 | 100 | Control | pre |
SA166820 | 68 | Control | pre |
SA166821 | 39 | Control | pre |
SA166822 | 234 | Control | pre |
SA166823 | 44 | Control | pre |
SA166824 | 164 | Control | pre |
SA166825 | 145 | Control | pre |
SA166826 | 36 | Control | pre |
SA166827 | 168 | Control | pre |
SA166828 | 16 | Control | pre |
SA166829 | 172 | Control | pre |
SA166830 | 237 | Control | pre |
SA166831 | 169 | Control | pre |
SA166832 | 54 | Control | pre |
SA166833 | 229 | Control | pre |
SA166834 | 78 | Control | pre |
SA166835 | 65 | Control | pre |
SA166836 | 55 | Control | pre |
SA166837 | 198 | Control | pre |
SA166838 | 219 | Control | pre |
SA166839 | 62 | Control | pre |
SA166840 | 228 | Control | pre |
SA166841 | 146 | Control | pre |
SA166842 | 57 | Control | pre |
SA166843 | 86 | Control | pre |
SA166844 | 176 | HDR | post |
SA166845 | 132 | HDR | post |
SA166846 | 157 | HDR | post |
SA166847 | 190 | HDR | post |
SA166848 | 166 | HDR | post |
SA166849 | 189 | HDR | post |
SA166850 | 153 | HDR | post |
SA166851 | 93 | HDR | post |
SA166852 | 41 | HDR | post |
SA166853 | 215 | HDR | post |
SA166854 | 89 | HDR | post |
SA166855 | 232 | HDR | post |
SA166856 | 223 | HDR | post |
Collection:
Collection ID: | CO001861 |
Collection Summary: | Spot urine collected before and after irradiation |
Sample Type: | Urine |
Storage Conditions: | -80℃ |
Treatment:
Treatment ID: | TR001881 |
Treatment Summary: | The VADER was designed to deliver controlled dose rates in the range 0.1 – 1 Gy/day to a cohort of up to 15 mice. The VADER uses ~0.5 Ci of retired 137Cs brachytherapy seeds that are arranged in two platters placed above and below a “mouse hotel”. The platters can be placed ~0.5 – 60 cm above and below the mouse hotel allowing implementation of time-variable dose rates. Offline dosimetry of the VADER was performed annually using a NIST traceable 10x6-6 ionization chamber (Radcal Corp., Monrovia, CA). Dose uniformity across the surface was measured using EBT3 film (Ashland, Covington, KY, USA) and the variation was 15% across the hotel. A lead and high-density concrete brick shield ensured minimal radiation doses to occupationally exposed personnel (operators) inside (< 0.1 mGy/wk) and outside the room (< 0.02 mGy/wk). The mouse hotel consists of an acrylic box (35 x 35 x 12 cm) allowing housing of ≤ 15 mice with bedding material and food/water ad libitum. Temperature (20 – 25°C), humidity (40 – 60%), airflow and lighting were fully controlled to required animal care standards (temperature/humidity sensor, HWg HTemp, TruePath Technologies Victor, NY). Environmental controls and monitoring were integrated into the mouse hotel for easy replacement in case of radiation damage. Mice were monitored in real time using a 180° fisheye ELP USB camera (Amazon). All animal experiments were approved by the Columbia University Institutional Animal Care and Use Committee (IACUC; approved protocol AAQ2410) and were conducted under all relevant federal and state guidelines. Male and female C57BL/6 mice ( Charles River Laboratories, Frederick, MD, USA) were irradiated in the VADER in two randomized batches (15 mice) loaded into mouse hotels (one hotel loaded into the VADER and one in the same room as a zero-dose control). Five mice per time point were irradiated in two back-to-back runs (run 1: 2, 3, or 5 d; run 2: 5, 20, or 30 d) to a total dose of 1 Gy (1 d), 2 Gy (2 d), 2.8 Gy (3 d), 4.1 Gy (5 d), 8.8 Gy (20 d), and 9.7 Gy (30 d) (Figure S1). Urine and serum were flash frozen and then stored at -80°C until shipped to Georgetown University Medical Center for analysis. |
Sample Preparation:
Sampleprep ID: | SP001874 |
Sampleprep Summary: | Samples were prepared and analyzed as previously described.18, 19 Briefly, serum (5 μl) was deproteinized (195 μl 66% cold acetonitrile [ACN]) with internal standards (2 μM debrisoquine [M+H]+ = 176.1188; 30 μM 4-nitrobenzoic acid [M-H]- = 166.0141), vortexed, incubated on ice (10 min), and centrifuged for 10 min (max speed, 4 °C). Urine (20 μl) was deproteinized (80 μl 50% cold ACN) and prepared as above. For urine and serum 1 μl of each sample were combined for a quality control (QC) sample. |
Combined analysis:
Analysis ID | AN002905 | AN002906 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | Reversed phase | Reversed phase |
Chromatography system | Waters Acquity | Waters Acquity |
Column | Waters Acquity BEH C18 (50 x 2.1mm,1.7um) | Waters Acquity BEH C18 (50 x 2.1mm,1.7um) |
MS Type | ESI | ESI |
MS instrument type | QTOF | QTOF |
MS instrument name | Waters Synapt G2 | Waters Synapt G2 |
Ion Mode | POSITIVE | NEGATIVE |
Units | peak area | peak area |
Chromatography:
Chromatography ID: | CH002154 |
Chromatography Summary: | Mobile phases consisted of the following: solvent A (water/0.1% formic acid [FA]), solvent B (ACN/0.1% FA), solvent C (isopropanol [IPA]/ACN (90:10)/0.1% FA). The gradient for urine was (solvent A and B) 4.0 min 5% B, 4.0 min 20% B, 5.1 min 95% B, and 1.9 min 5% B at a flow rate of 0.5 ml/min. The gradient for serum was (solvent A, B, and C) 4.0 min 98:2 A:B, 4.0 min 40:60 A:B, 1.5 min 2:98 A:B, 2.0 min 2:98 A:C, 0.5 min 50:50 A:C, and 1.0 min 98:2 A:B at a flow rate of 0.5 ml/min. |
Instrument Name: | Waters Acquity |
Column Name: | Waters Acquity BEH C18 (50 x 2.1mm,1.7um) |
Flow Gradient: | The gradient for urine was (solvent A and B) 4.0 min 5% B, 4.0 min 20% B, 5.1 min 95% B, and 1.9 min 5% B at a flow rate of 0.5 ml/min. The gradient for serum was (solvent A, B, and C) 4.0 min 98:2 A:B, 4.0 min 40:60 A:B, 1.5 min 2:98 A:B, 2.0 min 2:98 A:C, 0.5 min 50:50 A:C, and 1.0 min 98:2 A:B at a flow rate of 0.5 ml/min. |
Flow Rate: | 0.5 ml/min |
Solvent A: | 100% water; 0.1% formic acid |
Solvent B: | solvent B:100% acetonitrile; 0.1% formic acid solvent C:90% isopropanol/10% acetonitrile; 0.1% formic acid |
Chromatography Type: | Reversed phase |
MS:
MS ID: | MS002697 |
Analysis ID: | AN002905 |
Instrument Name: | Waters Synapt G2 |
Instrument Type: | QTOF |
MS Type: | ESI |
MS Comments: | Operating conditions for ESI were: capillary voltage 2.75 kV, cone voltage 30 V, desolvation temperature 500°C, desolvation gas flow 1000 L/Hr. |
Ion Mode: | POSITIVE |
MS ID: | MS002698 |
Analysis ID: | AN002906 |
Instrument Name: | Waters Synapt G2 |
Instrument Type: | QTOF |
MS Type: | ESI |
MS Comments: | Operating conditions for ESI were: capillary voltage 2.75 kV, cone voltage 30 V, desolvation temperature 500°C, desolvation gas flow 1000 L/Hr. |
Ion Mode: | NEGATIVE |