Our CMCR is focused on the development of medical countermeasures to assess, diagnose, and treat those exposed to radiation by developing (1) methods for rapid, high throughput assessment or measurement of radiation exposure through both bioassays and instruments, and (2) agents for mitigation and treatment of radiation effects with an emphasis on early and late side effects in non-hematopoietic tissues. Given both the urgent need to develop and validate medical countermeasures to seemingly imminent radiological and nuclear threats, and the dearth of available assessment tools or therapies, our short-term Center goal has been to develop and validate a number of therapeutic agents and radiation exposure assessment devices as quickly as possible, at least to the point of usefulness and availability for an emergency situation. Such a requirement is driven by the need for emergency/disaster response teams to be able to rapidly identify those who are contaminated with radioactive material and reassure those who are not, assess the extent/dose of radiation exposure, and administer appropriate treatment. Our expectation is to accelerate the development of our dosimeters and discriminators (methods of screening for radiation exposure which do not measure dose) as well as 2 or 3 of our most promising therapeutic agents that can be offered to victims (and rescue workers) to mitigate early and/or late non-hematopoietic effects.
Click here for info on BIODOSE 2008 at Dartmouth (Sept7-11): The 7th International Symposium on ESR Dosimetry and Applications
PROJECT 1
Project 1 has demonstrated early progress with a number of agents that may prove useful in radiation mitigation and/or treatment. These include EsA as a lung and skin radiation protector, which is undergoing acquisition of intellectual property (international patent). In addition, testing of customized Curcumin analogs and customized FGF analogs has suggested that these agents may provide both protection and mitigation of the acute gastrointestinal syndrome in addition to both early and late cutaneous radiation toxicity.
PROJECT 2
Cytokine profiles using bead arrays have generated a panel of cytokines and growth factors in the C57BL/6 mouse and these may provide information for biodosimetric analysis. Most exciting has been the demonstration that juvenile mice have greatly different responses than their more mature counterparts. This added complexity will be important as we attempt to develop agents that mitigate radiation toxicity for the general population. We believe this to be the first discovered difference in radiobiological marker response in a juvenile population.
PROJECT 3
The instrument at Dartmouth is being cloned so that comprehensive measurements can be made in a clinical situation. This instrument should be ready for routine operation on schedule at the close of year 2. In addition, finger-nail dosimetry using EPR appears promising, and unlike most biological measures is relatively stable in time and available without a lag time. The collection of samples should also be very simple and safe. Thus this approach will be studied further at Dartmouth and concurrently with additional technologies via a pilot project grant at Rochester.
PROJECT 4
The 3-D human bone marrow culture is essential to the support of MN-RET as radiation dose estimate in humans. It holds great promise as an ex vivo culture systems to investigate the potential effects by either mitigating agents or growth factors on human bone marrows.
PROJECT 5
An exciting development has been the detection and characterization of gamma-H2AX foci after irradiation at low doses. These studies can now be done by a number of methods including in vitro and in vivo models.
Recent CBARMFI Communications
CBARMFI Publications (2007-present)
1. Robert G Bristow, Hilmi Ozcelik, Farid Jalali, Norman Chan, and Danny
Vesprini. Homologous Recombination and Prostate Cancer: Prostate Cancer
as a Model for Novel DNA Repair Targets and Therapies. In Press, Radiotherapy
and Oncology, 2007.
2. Norman Chan, Michael Milosevic, Robert Bristow. Hypoxia, DNA Repair
and Prostate Cancer: New targets and New Strategies. In Press, Future
Oncology, 2007.
3. Chen Y., Hyrien O., Nowak I., Tsai Y., Wang N., Wilkins R., Ferrarotto
C., Dertinger S. Validation of high throughput micronucleus analysis
in peripheral reticulocytes for radiation biodosimetry. 13th International
Congress of Radiation Research July 7-12, San Francisco, 2007.
4. Demidenko E, Williams BB, Sucheta A, Dong R, and Swartz HM. Radiation
dose reconstruction from L-band n vivo EPR spectroscopy of intact teeth:
Comparison of methods. Radiation Measurements, in press (2007).
5. Eugene Demidenko, Benjamin B. Williams, Artur Sucheta, Ruhong Dong,
Harold M. Swartz. “Statistical Precision Assessment for In Vivo
EPR Tooth Dosimetry Using Inverse Regression and Confidence Interval,”
A Joint Conference of 12th In Vivo EPR Spectroscopy and Imaging and
9th International EPR Spin Trapping/Spin Labeling, Chicago, Illinois,
April 29-May 3, 2007.
6. Dertinger SD, Hyrien O, Chen Y. Flow cytometric scoring of radiation-induced
micronuclei: reticulocyte- and lymphocyte-based approaches. Environmental
Mutagen Society, Atlanta, Oct. 2007 (invited lecture).
7. Dertinger SD, MacGregor JT, Hyrien O, Chen Y. Micronucleated CD71-positive
reticulocytes: A cross-species bridging endpoint. 8th International
Symposium on Chromosomal Aberrations, Awaji Island, Hyogo, Japan, Oct.
2007 (invited lecture).
8. Dertinger SD, Miller RK, Brewer K, Smudzin T, Torous DK, Roberts
DJ, Avlasevich SL, Bryce SM, Sugunan S, Chen Y. Automated human blood
micronucleated reticulocyte measurements for rapid assessment of chromosomal
damage. Mutat Res. 2007;626(1-2):111-9.
9. Dertinger SD, Tsai Y, Nowak I, Hyrien O, Sun H, Bemis JC, Torous
DK, Keng P, Palis J, Chen Y. Reticulocyte and micronucleated reticulocyte
responses to gamma irradiation: dose-response and time-course profiles
measured by flow cytometry. Mutat Res 634:119-125, 2007.
10. S. Dertinger: Platform Presentation, 2007 Environmental Mutagen
Society National Meeting: "Flow Cytometric Scoring of Radiation-Induced
Micronuclei: Reticulocyte- and Lymphocyte-Based Approaches"
11. S. Dertinger. Society of Toxicology, 2008 National Meeting: "Rapid
Assessment of the Effects of Radiation Exposure via Flow Cytometric
Analysis of Whole Blood"
12. Ruhong Dong, Artur Sucheta, Eugene Demidenko, Benjamin B. Williams,
Maciej Kmiec, Gregory Burke, Piotr Lesniewski, Firdus F. Gubaydullin,
Andres Ruuge, Harold M. Swartz. “Experimental Procedure to Improve
Rapid and Accurate Positioning of the Resonator on the Tooth: In Vivo
Tooth Dosimetry.” A Joint Conference of 12th In Vivo EPR Spectroscopy
and Imaging and 9th International EPR Spin Trapping/Spin Labeling, Chicago,
Illinois, April 29-May 3, 2007.
13. R. Dong, A. Sucheta, E. Demidenko, B.B. Williams, M. Kmiec, G. Burke,
P. Lesniewski, F.F. Bubaydullin, A. Ruuge, H.M. Swartz. “Rapid
and Accurate In Vivo Dosimetry: Experimental Procedure for Positioning
the Resonator.” 13th International Congress of Radiation Research.
San Francisco, California. July 7-11, 2007.
14. J.N. Finkelstein, J.P. Williams, E. Hernady, C. Reed, P. Okunieff,
C.J. Johnston. Early alterations in pulmonary interleukin expression
and cellular responses after low dose radiation. 13th International
Congress of Radiation Research, San Francisco, July 8-12, 2007.
15. Ann B. Flood, H.M. Swartz, Shayan Bhattacharyya, and Javier Nicolalde,
“Implementing EPR Dosimetry for Life-Threatening Incidents: Factors
Beyond Technical Performance.” Radiation Measurements. In press
(2007).
16. Eric Hernady, Carl Johnston, Christina Reed, Sally Thurston, Jacob
N. Finkelstein, Jacqueline P. Williams. Late inflammatory response following
low dose radiation to the lung. Submitted to 54th Annual Meeting of
Radiation Research Society, Boston, September 20-24, 2008.
17. R. P Hill. P. Kaspler, A.M. Griffin, B. O’Sullivan, C. Catton,
H. Alasti, A Abbas, M Heydarian, P. Ferguson, J.S. Wunder and R. S.
Bell. Studies of the in vivo radiosensitivity of human skin fibroblasts.
Conditionally accepted. Radiotherapy and Oncology 2007.
18. Ivannikov, S. Toyoda, M. Hoshi, et al. “Interlaboratory Comparison
on Tooth Enamel Dosimetry on Semipalatinsk Region: Part 1, General View,”
Radiation Measurements. In Press (2007).
19. Ivannikov, S. Toyoda, M. Hoshi, et al. “Interlaboratory Comparison
on Tooth Enamel Dosimetry on Semipalatinsk Region: Part 2. Effects of
Spectra Processing.” Radiation Measurements. In Press (2007).
20. C.J. Johnston, J.P. Williams, E. Hernady, J.N. Finkelstein. Radiation
injury during postnatal lung development. 13th International Congress
of Radiation Research, San Francisco, July 8-12, 2007.
21. Carl J. Johnston, Eric Hernady, Christina Reed, Bruce M. Fenton,
Jacob N. Finkelstein, Jacqueline P. Williams. Role of IL-1 and inflammatory
cell recruitment in radiation-induced pulmonary late effects. Submitted
to Radiation Research. Under revision.
22. Carl J. Johnston, Eric Hernady, Christina Reed, Sally Thurston,
Jacob N. Finkelstein, and Jacqueline P. Williams, Ph.D. Early alterations
in pulmonary interleukin expression: surrogate markers in adult versus
children following a terrorist event. Submitted to International Journal
of Radiation Oncology, Biology and Physics. Under review.
23. Carl Johnston, Eric Hernady, Christina Reed, Sally Thurston, Thomas
Morgan, Jacqueline P. Williams, Jacob N. Finkelstein. Pulmonary response
to internal contamination: a model for a RDD. Submitted to 54th Annual
Meeting of Radiation Research Society, Boston, September 20-24, 2008.
24. C.J. Johnston, J.N. Finkelstein, E. Hernady, C. Reed, and J.P. Williams.
Radiation combined injury: radiation exposure in combination with infection.
Submitted to 5oth Annual Meeting of American Society for Therapeutic
Radiology and Oncology, Boston, September 20-24, 2008.
25. Nowak I., Hyrien O., Chen Y. Micronucleus (MN) versus nucleoplasmic
bridge (NPB) assessment for radiation biodosimetry in human lymphocytes.
13th International Congress of Radiation Research, July 7-12, San Francisco,
2007.
26. Okunieff P, Yuhchyau Chen, David J. Maguire, Amy K. Huser. Molecular
Markers of Radiation-related Normal Tissue Toxicity. Clinical and Metastasis
Reviews. In press (2008).
27. Amber Rinderknecht: Biodistribution in rat of Au nanoparticles as
measured by neutron activation. Golden Horseshoe, McMaster University,
August 30, 2007.
28. A.A. Romanyukha, C.A. Mitchell, D.A. Schauer, L. Romanyukha and
H.M. Swartz. “Q-Band EPR Biodosimetry in Tooth Enamel Microsamples:
Feasibility Test and Comparison with X Band.” Health Physics.
In Press (2007).
29. A.A. Romanyukha, F. Trompier, B. LeBlanc, C. Calas, I. Clairand,
C. Mitchell, James G. Smirniotopoulos, H. Swartz, “EPR Dosimetry
in Chemically Treated Fingernails.” Radiation Measurements. In
Press (2007).
30. S. Rosenstein, K. D. Held, S. Rockwell, J. Williams, E. M. Zeman.
Survey of Radiation Biology Educators in U.S. and Canadian Radiation
Oncology Residency Programs. ASTRO 2008.
31. Sato, B.A. Filas, S.S. Eaton, G.R. Eaton, A.A. Romanyukha, R. Hayes,
and A.M. Rossi, “Electron Spin Relaxation of Radicals in Irradiated
Tooth Enamel and Synthetic Hydroxyapatite.” Radiation Measurements.
In Press (2007).
32. D.A. Schauer, A. Iwasaki, A.A. Romanyukha, H.M. Swartz and S. Onori,
"Electron Paramagnetic Resonance (EPR) in Medical Dosimetry,"
Radiation Measurements. In Press (2007).
33. S.L. Simon, I. Bailiff, A. Bouville, P. Fattibene, R.A. Kleinerman,
D.C. Lloyd, S.W.S. McKeever, A. Romanyukha, A.V. Sevan'kaev, J.D. Tucker,
“Methods to Evaluate Radiation Doses at Long Times After Exposure.”
Radiation Measurements. In Press (2007).
34. Artur Sucheta, Ruhong Dong, Maciej Kmiec, Gregory Burke, Andres
Ruuge, Piotr Lesniewski, Eugene Demidenko, Benjamin B. Williams, Firdus
Gubaydullin, and Harold M. Swartz. “Improvements in Hardware,
Experimental Procedures, and Data Analysis for Rapid and Accurate In
Vivo Tooth Dosimetry.” A Joint Conference of 12th In Vivo EPR
Spectroscopy and Imaging and 9th International EPR Spin Trapping/Spin
Labeling, Chicago, Illinois, April 29-May 3, 2007.
35. H.M. Swartz “In Vivo EPR as a New Clinical Tool: Current and
Future Applications that Provide Unique Clinically Useful Data. Seminar
at the GSF – National Research Center for Environment and Health.
Munich, Germany, February 27, 2007.
36. H.M. Swartz “In Vivo EPR as a New Clinical Tool: Current and
Future Applications that Provide Unique Clinically Useful Data.”
Seminar at the Catholic University of Louvain, Brussels, Belgium. March
2, 2007.
37. H.M. Swartz “Measurement of Clinically Significant Exposures
to Ionizing Radiation with Sufficient Speed and Accuracy to Enable Triage
of Large Numbers of People.” Invited Lecturer: H.M. Swartz. 17th
Nuclear Medical Defense Conference of the Bundeswehr Institute of Radiobiology
in Munich, Germany, February 28, 2007.
38. H.M. Swartz “Overview of In Vivo EPR for Use in Human Subjects.
Plenary Session. H.M. Swartz. Invited Speaker. A Joint Conference of
12th In Vivo EPR Spectroscopy and Imaging and 9th International EPR
Spin Trapping/Spin Labeling, Chicago, Illinois, April 29-May 3, 2007.
39. H.M. Swartz, A. Sucheta, R. Dong, E. Demidenko, B. Williams, P.
Lesniewski, M. Kmiec and Y. Sakata. “Achieving Requirements for
Dosimetry for Management of Potential Radiation Exposures to a Large
Population with EPR Techniques.” 13th International Congress of
Radiation Research. San Francisco, California. July 7-11, 2007.
40. Harold M. Swartz, Greg Burke, M. Coey, Eugene Demidenko, Ruhong
Dong, Oleg Grinberg, James Hilton, Akinori Iwasaki, Piotr Lesniewski,
Maciej Kmiec, Kai-Ming Lo, R. Javier Nicolalde, Andres Ruuge, Yasuko
Sakata, Artur Sucheta, Tadeusz Walczak, Benjamin B. Williams, Chad Mitchell,
Alex Romanyukha, David A. Schauer, "In Vivo EPR for Dosimetry."
Radiation Measurements. In Press (2007).
41. Harold M. Swartz. “Introduction to the Symposium on EPR Dosimetry:
Achieving Requirements for Dosimetry for Management of Potential Radiation
Exposures to a Large Population.” A Joint Conference of 12th In
Vivo EPR Spectroscopy and Imaging and 9th International EPR Spin Trapping/Spin
Labeling, Chicago, Illinois, April 29-May 3, 2007.
42. S. Toyoda, A. Romanyukha, Y. Hino, S. Itano, H. Imata, O. Tarasov
and M. Hoshi, “Effect of Chemical Treatment on ESR Dosimetry of
Cow Teeth: Application to the samples from Southern Urals,” Radiation
Measurements. In Press (2007).
43. Tsai Y, Ferrarotto C, Wang N, Wilkins R, Chen Y. Optimizing cytogenetic
analysis for radiation-induced chromosomal aberration in C57Bl/6 Mice.
13th International Congress of Radiation Research, July 7-12, San Francisco,
2007 (meeting abstract).
44. F. Trompier, L. Kornak, C. Calas, A. Romanyukha, B. LeBlanc, I.
Clairand, C. A. Mitchell, H. Swartz, “Protocol for Emergency EPR
Dosimetry in Fingernails.” Radiation Measurements. In Press (2007).
45. Veenema T.G., Hellman B.D., Walden B., Feinstein N., Williams J.P.
Factors Affecting Hospital-Based Nurses’ Willingness to Respond
to a Radiation Emergency: Forthcoming from the American Journal of Disaster
Medicine (2008).
46. Benjamin B. Williams, Artur Sucheta, Ruhong Dong, Yasuko Sakata,
Akinori Iwasaki, Gregory Burke, Oleg Grinberg, Piotr Lesniewski, Maciej
Kmiec, Harold M. Swartz. “Experimental Procedures for Sensitive
and Reproducible In Situ EPR Tooth Dosimetry,” Radiation Measurements.
In Press (2007).
47. J. P. Williams, C. Johnston, E. Hernady, C. Reed, J. N. Finkelstein.
Potential use of early cytokine changes as surrogate markers in adults
versus children following a terrorist event. 49th Annual Meeting of
the American Society for Therapeutic Radiology and Oncology, Los Angeles,
October 28-November 1, 2007.
48. J.P. Williams, C. Johnston, E. Hernady, C. Reed, J.N. Finkelstein.
Cytokines and radiation treatment: mitigators or mitigating targets.
13th International Congress of Radiation Research, San Francisco, July
8-12, 2007 (invited speaker).
49. Zhang, Hengshan, Weimin Sun, Shanmin Yang, Mei Zhang, Wei Wang,
Chaomei Liu, Kunzhong Zhang, Steven Swarts, Bingrong Zhang, Bruce M.
Fenton, Peter Keng, David Maguire, Paul Okunieff, and Lurong Zhang.
B1 Sequence-based real-time Quantitative PCR: A sensitive method for
direct measurement of mouse plasma DNA levels after gamma irradiation.
Submitted to Int J Radiat Oncol Biol Phys (2008).
50. Hengshan Zhang, Weimin Sun, Shanmin Yang, Wei Wang, Bingrong Zhang,
Chaomei Liu, Jianjun Wang, Steven Swarts, Mei Zhang, Bruce Fenton, Peter
Keng, Paul Okunieff and Lurong Zhang: A sensitive assay for quantitative
measurement of plasma DNA: Application in radiation oncology. Proc.
Ann. Am. Assoc. Cancer Res. 2007
