Summary of Study ST001790

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.

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Study IDST001790
Study TitleEffect of external low-dose rate radiation on mouse biofluid metabolomic signatures (part I)
Study SummaryAn 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 NamePannkuk
First NameEvan
Address3970 Reservoir Rd, NW New Research Building E504
Emailelp44@georgetown.edu
Phone2026875650
Submit Date2021-05-11
Raw Data AvailableYes
Raw Data File Type(s)raw(Waters)
Analysis Type DetailLC-MS
Release Date2021-12-15
Release Version1
Evan Pannkuk Evan Pannkuk
https://dx.doi.org/10.21228/M8R102
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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:SU001867
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6
Gender:Male
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
SA16656556Control post
SA166566194Control post
SA166567112Control post
SA166568138Control post
SA16656962Control post
SA166570134Control post
SA16657194Control post
SA166572204Control post
SA166573205Control post
SA16657450Control post
SA16657551Control post
SA16657664Control post
SA16657793Control post
SA16657866Control post
SA166579167Control post
SA166580179Control post
SA166581146Control post
SA166582147Control post
SA166583154Control post
SA16658475Control post
SA166585180Control post
SA16658667Control post
SA16658786Control post
SA166588185Control post
SA166589184Control post
SA166590182Control post
SA16659165Control post
SA16659244Control post
SA16659343Control post
SA166594236Control post
SA166595229Control post
SA166596232Control post
SA166597234Control post
SA166598255Control post
SA166599119Control post
SA166600102Control post
SA16660113Control post
SA166602113Control post
SA16660340Control post
SA16660441Control post
SA16660542Control post
SA166606207Control post
SA16660738Control post
SA16660810Control post
SA166609107Control post
SA166610210Control post
SA16661135Control post
SA166612141Control pre
SA166613127Control pre
SA166614132Control pre
SA1666159Control pre
SA166616131Control pre
SA166617139Control pre
SA166618117Control pre
SA166619121Control pre
SA166620115Control pre
SA166621191Control pre
SA166622247Control pre
SA166623238Control pre
SA166624230Control pre
SA166625225Control pre
SA166626250Control pre
SA166627251Control pre
SA166628220Control pre
SA166629254Control pre
SA166630253Control pre
SA166631223Control pre
SA166632218Control pre
SA166633168Control pre
SA166634165Control pre
SA166635155Control pre
SA166636186Control pre
SA166637190Control pre
SA166638197Control pre
SA166639196Control pre
SA166640195Control pre
SA166641152Control pre
SA166642133Control pre
SA16664382Control pre
SA166644108Control pre
SA16664589Control pre
SA16664624Control pre
SA16664799Control pre
SA16664895Control pre
SA16664968Control pre
SA16665063Control pre
SA16665139Control pre
SA16665248Control pre
SA16665337Control pre
SA16665457Control pre
SA16665561Control pre
SA16665623Control pre
SA16665727Control pre
SA16665815Control pre
SA16665912Control pre
SA166660203HDR post
SA166661171HDR post
SA166662151HDR post
SA166663153HDR post
SA166664216HDR post
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Collection:

Collection ID:CO001860
Collection Summary:Spot urine collected before and after irradiation
Sample Type:Urine
Storage Conditions:-80℃

Treatment:

Treatment ID:TR001880
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:SP001873
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.
Processing Storage Conditions:-80℃

Combined analysis:

Analysis ID AN002903 AN002904
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 S QTOF Waters Synapt G2 S QTOF
Ion Mode POSITIVE NEGATIVE
Units peak area peak area

Chromatography:

Chromatography ID:CH002153
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:MS002695
Analysis ID:AN002903
Instrument Name:Waters Synapt G2 S QTOF
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:MS002696
Analysis ID:AN002904
Instrument Name:Waters Synapt G2 S QTOF
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
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