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Task Last Updated: 08/14/2008 
Division Name: Human Research 
Program/Discipline: HUMAN RESEARCH 
Element/Subdiscipline: Radiation health 
Project Title: NSCOR: Radiation Leukemogenesis 
Joint Agency Name:  
PI Name: Ullrich, Robert   PI Phone: 409-747-1935  
PI Email: bullrich@utmb.edu  Fax:  
PI Organization Type: UNIVERSITY 
Organization Name: University of Texas Medical Branch 
PI Address 1: 301 University Blvd 
PI Address 2: Comprehensive Cancer Center, MS 1048 
PI Web Page:  
City: Galveston State: TX Zip Code: 77555-5302 Congressional District: 14
Comments: NOTE: PI moved to UTMB from Colorado State University in late 2008 (6/2009) 
Project Type: GROUND  Solicitation: NSCOR 03-OBPR-02 
Start Date: 10/01/2003  End Date: 07/30/2009 
Fiscal Year: 2008     
No. of Post Docs: 1  No. of PhD Degrees: 2 
No. of PhD Candidates: 4  No. of Master' Degrees:  
No. of Master's Candidates: 0  No. of Bachelor's Degrees:  
No. of Bachelor's Candidates: 0  Monitoring Center: JSC 
Contact Monitor: Cucinotta, Francis   Contact Phone: 281-483-0968 
Contact Email: francis.a.cucinotta@nasa.gov     
Flight Program:  
Flight Assignment: NOTE: End date changed to 7/30/2009 per J. Dardano/JSC (10/2009)

NOTE: Received NCE to 12/31/2008 (from 9/30/2008) per J. Dardano/JSC (9/2008)

 
Key Personnel Changes/Previous PI:  
COI Name: COI Institution:
Bailey, Susan   Colorado State University 
Bedford, Joel   Colorado State University 
Belmont, John   Baylor College of Medicine 
Cai, Wei-Wen   Baylor College of Medicine 
Ehrhart, E.J.   Colorado State University 
Nagarajan, Lalitha    U.T., M.D. Anderson. Cancer Center  
Story, Michael   University of Texas, M. D. Anderson Cancer Center  
Weil, Michael   U.T., M.D. Anderson. Cancer Center 
Grant/Contract No.: NAG9-1569 
Performance Goal No.:  
Performance Goal Text:

 
Task Description:  The goal of this program is to provide information required to develop a rational scientific basis for estimation of risks for leukemogenesis in humans from exposure to radiation during space flight. This will be accomplished using several coordinated research activities. A key activity will be to develop quantitative data on the relative leukemogenic effectiveness of specific HZE particles and of high-energy protons compared with gamma rays in a mouse model of radiation-induced acute myeloid leukemia (AML). Extrapolation of risks from this mouse model to risks in humans requires additional information, and a major component of research activities in this program are designed to provide such information. A major research effort of this program is focused on studies of cellular and molecular mechanisms and processes involved in radiation-induced AML. These studies will not only improve the basic understanding of the pathogenesis of AML but will also provide information on cellular and molecular biomarkers that may be useful in predicting individuals at increased risk. These activities will focus on the use of molecular and molecular cytogenetic approaches, the development of new model systems, and comparative analyses of murine and human AML to facilitate the translation of results obtained in mice to human AMLs. Problems of extrapolation are not limited to biological factors. There are clear dosimetric differences that also must be considered when extrapolating data obtained from mouse studies to human risks. To address these issues this project also has an important physics and dosimetry component that includes modeling of dose to target cells in murine and human bone marrow.

 
Research Impact/Earth Benefits: This research provides information on risks from exposure to ionizing radiation and mechanisms of carcinogenesis. It has also provided insight into potential approaches to chemoprevention of radiation damage.

Task Progress: Key Findings:

a) In mice, 1 GeV/n 56Fe ions do not appear to be substantially more effective than gamma rays for induction of AML

b) In contrast, 56Fe irradiated mice had much higher risk for hepatocellular carcinoma than gamma ray irradiated mice

c) Chromosome 2 deletions detected in bone marrow cells one month post-irradiation may be a biomarker for AML risk

d) There are no apparent differences between 56Fe and gamma ray induced AML at the cytogenetic or molecular level

 
Bibliography Type: Description: (Last Updated: 02/04/2010)
Articles in Peer-reviewed Journals Williams ES, Stap J, Essers J, Ponnaiya B, Luijsterburg MS, Krawczyk PM, Ullrich RL, Aten JA, Bailey SM. "DNA double-strand breaks are not sufficient to initiate recruitment of TRF2." Nat Genet. 2007 Jun;39(6):696-8; author reply 698-9. PMID: 17534357 , Jun-2007
Articles in Peer-reviewed Journals Carsten RE, Bachand AM, Bailey SM, Ullrich RL. "Resveratrol reduces radiation-induced chromosome aberration frequencies in mouse bone marrow cells." Radiat Res. 2008 Jun;169(6):633-8. PMID: 18494544 , Jun-2008
Articles in Peer-reviewed Journals Ding LH, Xie Y, Park S, Xiao G, Story MD. "Enhanced identification and biological validation of differential gene expression via Illumina whole-genome expression arrays through the use of the model-based background correction methodology." Nucleic Acids Res. 2008 Jun;36(10):e58. Epub 2008 May 1. PMID: 18450815 , Jun-2008
Articles in Peer-reviewed Journals Hagelstrom RT, Askin KF, Williams AJ, Ramaiah L, Desaintes C, Goodwin EH, Ullrich RL, Bailey SM. "DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals." Oncogene. 2008 Aug 4. [Epub ahead of print] PMID: 18679419 , Aug-2008
Articles in Peer-reviewed Journals Peng Y, Brown N, Finnon R, Warner CL, Liu X, Genik PC, Callan MA, Ray FA, Borak TB, Badie C, Bouffler SD, Ullrich RL, Bedford JS, Weil MM. "Radiation Leukemogenesis in Mice: Loss of PU.1 on Chromosome 2 in CBA/Ca and C57BL/6 Mice after Irradiation with 1 GeV/n 56Fe Ions, X- or gamma-rays. Part I. Experimental Observations." Submitted Radiation Research, August 2008. , Aug-2008
Articles in Peer-reviewed Journals Peng Y, Borak TB, Bouffler SD, Ullrich RL, Weil MM, Bedford JS. "Radiation Leukemogenesis in Mice: Loss of PU.1 on Chromosome 2 in CBA/Ca and C57BL/6 Mice after Irradiation with 1 GeV/n 56Fe Ions or gamma-Rays. Part II. Theoretical Considerations Based on Microdosimetry and the Initial Induction of Chromosome Aberrations." Submitted Radiation Research, August 2008. , Aug-2008
Articles in Peer-reviewed Journals Weil MM, Bedford JS, Erhart EJ, Ray FA, Genik PC, Fallgren C, Ullrich RL. "Incidence of acute myeloid leukemia and hepatocellular carcinoma in 1 GeV/n 56Fe irradiated mice." Submitted Radiation Research, August 2008. , Aug-2008
Patents 61/036,399. Pending, March 2008. Mar-2008 Carsten R, Ullrich R. "Reserveratrol pre and post exposure radioprotectant."
Patents 61/050,251. Pending, May 2008. May-2008 Carsten R, Ullrich R. "Grape as a Radioprotectant."