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Assessing the Biological Effects from Low Dose Exposures Similar to
Medical and Occupational Doses
Nghi PhanPh.D. Candidate
McMaster University
GreenhouseGases
http://antwrp.gsfc.nasa.gov/apod/ap001127.html
http://antwrp.gsfc.nasa.gov/apod/ap001127.html
Only, when Hell freezes over…
December 17, 2008
Radiation is Everywhere
Background Radiation
Reproduced without
permission from Radiobiology for the Radiology, 6th
Ed.
<2 mSv
5‐30 mSv
13‐70 mSv
100‐250 mSv
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
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?
Oxidative Stress
H2
O2O2
.‐
OH. OH.
H2
O2O2
.‐
Study Outline
• Effects of a single 20 mSv exposure
• Effects of repeat 20 mSv exposures
17‐weeks old
A Single CT ScanCT scan: 27 weeks old
Dose: ~20 mSv
Repeated CT Scans CT Scan: 17 weeks
Duration: 2x/wk/10wks
Dose: ~20 mSv
Total Dose: ~400 mSv
Study Outline
• Investigated– Genetic damage to stem cells
– DNA damage (yH2AX)
– Cell death via apoptosis
Reticulocyte FormationErythroblast(Bone Marrow)
Enucleation
Reticulocyte(Blood)
43 hrs
DSBx Micronucleus
Micronucleated‐Reticulocyte Formation
Erythroblast(Bone Marrow)
x EnucleationMN remains
x
MN‐RET
Marker of genotoxicity
High MN‐Ret = high genotoxicity→ bad thing
Results
n = 5 mice per dose
Results
n = 24, 27 w.o. male C57Bl/6 mice
p = 0.018
Results
n = 24, 27 w.o. male C57Bl/6 mice
p = 0.018
p = 0.093
Gamma H2AX Foci
• correlates to DNA damage• association with cancer risk?
SS LIN
Flow Cytometry
0 1 2
0 Sv
2 Sv
Results
n = 5, 7‐8 w.o. female p53+/+
micen = 8, 27 w.o. male C57Bl/6 mice
Results
n = 26, 27 w.o. male C57Bl/6
mice
Cell Death•
FLICA binds to activated Caspase 3 & 7
•
7AAD enters membrane‐compromised cells and binds to DNA
Results
n = 8, 27 w.o. male C57Bl/6 mice
Results
n = 26, 27 w.o. male C57Bl/6
mice
Single vs. Repeated CT Scans• “Snapshot”
phenomenon
En
dp
oin
t L
eve
ls
Endpoint vs. Time
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
Current & Future Directions
• Currently, studying the lifetime health and cancer risks of low dose exposures.
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)
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´
mie
Nationale
de Me´
decine, Institut
de France ‐Academie
des Sciences (March
30, 2005) Tubiana
M, Aurengo
A, Averbeck
D, Bonnin
A, Le Guen
B, Masse R, Monier
R, Valleron
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
430:307‐313.
Papastefanou, C. (2007) Radiation dose from cigarette tobacco. Radiation Protection Dosimetry
123(1):68–73.
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
of
Epidemiology 2007;36:1126–1135.