Nghi Phan investigated the biological effects of low dose radiation exposures similar to medical and occupational doses. Specifically, Phan assessed genetic damage, DNA damage, and cell death in mice exposed to a single 20 mSv dose, similar to a CT scan, and repeated 20 mSv exposures over 10 weeks for a total of 400 mSv. The study found evidence of genetic damage and DNA damage from both single and repeated exposures. Repeated exposures did not increase levels of chromosomal damage or cell death compared to spontaneous levels, but may induce an adaptive response. The results indicate assays can detect effects below 20 mSv and differences exist between single and repeated low dose exposures.

1. Assessing the Biological Effects
from Low Dose Exposures Similar to
Medical and Occupational Doses
Nghi Phan
Ph.D. Candidate
McMaster University

2. Greenhouse
Gases

5. http://antwrp.gsfc.nasa.gov/apod/ap001127.html

6. http://antwrp.gsfc.nasa.gov/apod/ap001127.html

7. Only, when Hell freezes over…
December 17, 2008

10. Radiation is Everywhere

11. Background Radiation
Reproduced without permission from Radiobiology for the Radiology, 6th
Ed.
<2 mSv
5‐30 mSv
13‐70 mSv
100‐250 mSv

12. 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

13. 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?

14. Oxidative Stress
H2O2
O2
.‐
OH. OH.
H2O2
O2
.‐

15. Study Outline
• Effects of a single 20 mSv exposure
• Effects of repeat 20 mSv exposures
17‐weeks old

16. A Single CT Scan
CT scan: 27 weeks old
Dose: ~20 mSv

17. Repeated CT Scans
CT Scan: 17 weeks
Duration: 2x/wk/10wks
Dose: ~20 mSv
Total Dose: ~400 mSv

18. Study Outline
• Investigated
– Genetic damage to stem cells
– DNA damage (yH2AX)
– Cell death via apoptosis

19. Reticulocyte Formation
Erythroblast
(Bone Marrow)
Enucleation
Reticulocyte
(Blood)
43
hrs

20. DSBx Micronucleus
Micronucleated‐Reticulocyte Formation
Erythroblast
(Bone Marrow)
x Enucleation
MN remains
x
MN‐RET
Marker of genotoxicity
High MN‐Ret = high genotoxicity
→ bad thing

21. Results
n = 5 mice per dose

22. Results
n = 24, 27 w.o. male C57Bl/6 mice
p = 0.018

23. Results
n = 24, 27 w.o. male C57Bl/6 mice
p = 0.018
p = 0.093

24. Gamma H2AX Foci
• correlates to DNA damage
• association with cancer risk?
SS LIN
Flow Cytometry
0 1 2
0 Sv
2 Sv

25. Results
n = 5, 7‐8 w.o. female p53+/+ mice
n = 8, 27 w.o. male C57Bl/6 mice

26. Results
n = 26, 27 w.o. male C57Bl/6 mice

27. Cell Death
• FLICA binds to activated Caspase 3 & 7
• 7AAD enters membrane‐compromised cells and binds to DNA

28. Results
n = 8, 27 w.o. male C57Bl/6 mice

29. Results
n = 26, 27 w.o. male C57Bl/6
mice

30. Single vs. Repeated CT Scans
• “Snapshot” phenomenonEndpointLevels
Endpoint vs. Time

31. 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

32. Current & Future Directions
• Currently, studying the lifetime health and
cancer risks of low dose exposures.

33. 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)

34. References
BEIR 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.