arps2010 prez phan -final
TRANSCRIPT
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Assessing the Biological Effects from Low Dose Exposures Similar to
Medical and Occupational Doses
Nghi PhanPh.D. Candidate
McMaster University
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GreenhouseGases
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http://antwrp.gsfc.nasa.gov/apod/ap001127.html
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http://antwrp.gsfc.nasa.gov/apod/ap001127.html
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Only, when Hell freezes over…
December 17, 2008
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Radiation is Everywhere
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Background Radiation
Reproduced without
permission from Radiobiology for the Radiology, 6th
Ed.
<2 mSv
5‐30 mSv
13‐70 mSv
100‐250 mSv
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Relevance
• Radiation Worker Limit: 20 mSv/year averaged over 5 years
• 15 Country Study ‐
407,391 nuclear industry workers monitored ‐
• E. Cardis et al
RADIATION RESEARCH 167, 396–416 (2007)
• Avg. Lifetime Dose for Nuclear Power Worker = 19.4 mSv
• Whole Body CT scans average: 20 mSv
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What about the Biology?
• Assessed the effects of 20 mSv– Radiation Worker annual dose limit
– Full Body CT Scan Dose
• Biological Effects…– Genetic damage to stem cells?
– DNA damage?
– Cell death?
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Oxidative Stress
H2
O2O2
.‐
OH. OH.
H2
O2O2
.‐
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Study Outline
• Effects of a single 20 mSv exposure
• Effects of repeat 20 mSv exposures
17‐weeks old
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A Single CT ScanCT scan: 27 weeks old
Dose: ~20 mSv
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Repeated CT Scans CT Scan: 17 weeks
Duration: 2x/wk/10wks
Dose: ~20 mSv
Total Dose: ~400 mSv
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Study Outline
• Investigated– Genetic damage to stem cells
– DNA damage (yH2AX)
– Cell death via apoptosis
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Reticulocyte FormationErythroblast(Bone Marrow)
Enucleation
Reticulocyte(Blood)
43 hrs
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DSBx Micronucleus
Micronucleated‐Reticulocyte Formation
Erythroblast(Bone Marrow)
x EnucleationMN remains
x
MN‐RET
Marker of genotoxicity
High MN‐Ret = high genotoxicity→ bad thing
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Results
n = 5 mice per dose
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Results
n = 24, 27 w.o. male C57Bl/6 mice
p = 0.018
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Results
n = 24, 27 w.o. male C57Bl/6 mice
p = 0.018
p = 0.093
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Gamma H2AX Foci
• correlates to DNA damage• association with cancer risk?
SS LIN
Flow Cytometry
0 1 2
0 Sv
2 Sv
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Results
n = 5, 7‐8 w.o. female p53+/+
micen = 8, 27 w.o. male C57Bl/6 mice
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Results
n = 26, 27 w.o. male C57Bl/6
mice
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Cell Death•
FLICA binds to activated Caspase 3 & 7
•
7AAD enters membrane‐compromised cells and binds to DNA
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Results
n = 8, 27 w.o. male C57Bl/6 mice
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Results
n = 26, 27 w.o. male C57Bl/6
mice
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Single vs. Repeated CT Scans• “Snapshot”
phenomenon
En
dp
oin
t L
eve
ls
Endpoint vs. Time
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Conclusions• Assays capable of detecting < 20 mSv• Differences exist between Single and
Repeated CT scans• Repeated CT scans (total dose: 400
mSv) ‐
do not increase spontaneous levels of
chromosomal damage & cell death‐
can induce an adaptive response
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Current & Future Directions
• Currently, studying the lifetime health and cancer risks of low dose exposures.
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Thank you• Boreham Lab
‐
Mary Ellen Bahen‐
Lisa LaFramboise
‐Nicole McFarlane‐ Caitlin Mills‐ Kristina Taylor
• Parise Group• NSERC ‐
CGS
• CIHR ‐
Vanier• DOE ‐
Low Dose Research Program
(DE‐FG02‐07ER64343)
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ReferencesBEIR VII (National Research Council of the National Academies of
USA). Health risk from exposure to low
levels of ionizing radiation. Pre‐publication version. July 2005.
Cadis, E. et al. (2007) The 15‐Country Collaborative Study of Cancer Risk among Radiation Workers in the
Nuclear Industry: Estimates of Radiation‐Related Cancer Risks. Radiation Research
167:396–416.
Joint Report no. 2, Acade´
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30, 2005) Tubiana
M, Aurengo
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AJ, de
Vathaire
F. Dose–effect relationships and the estimation of the carcinogenic effects of low doses of
ionizing radiation. (http://www.academiemedecine.fr/actualites/ rapports.asp) Edition Nucleon (Paris
2005) ISBN 2‐84332‐018‐6
Kiefer J. (1999) Radiation risk in manned space flights. Mutation Research
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Papastefanou, C. (2007) Radiation dose from cigarette tobacco. Radiation Protection Dosimetry
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Vrijheid, M. et al. (2007) Mortality from diseases other than cancer following low doses of ionizing
radiation: results from the 15‐Country Study of nuclear industry workers. International Journal
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Epidemiology 2007;36:1126–1135.