The cancer risk and associated public concern with exposures to alpha-emitting radionuclides, such as americium, plutonium, thorium, radium and others is well recognized. Current protection models are based largely on statistical assumptions with little biological data. We have developed biokinetic models that fit the experimental data, and will now test these models in the human and determine the localization, distribution and dosimetry of plutonium in archived skeletal tissues now available from Russian nuclear workers. Both experimental and human data will be used to extend our current biokinetic, dosimetric and risk models to the human.
The aims are: 1) To determine in canine materials the deposition and local radiation doses to tissues and cells as a function of time after exposure to plutonium. Neutron induced (NIAR) and conventional autoradiographic methods will be used. A biokinetic model will be constructed. 2) To develop an """"""""age quality factor"""""""" for exposures to plutonium. Our studies demonstrate important age-dependent biological determinants of nuclide uptake, retention and subsequent risk. These include bone growth, bone remodeling and hematopoiesis and vascularization. 3) The localization, distribution and radiation doses to tissues and cells from 239-Pu will be determined in human tissues using NIAR. Materials will be obtained from archives of both U.S. and more highly exposed Russian workers. 4) To correlate worker exposure and occupational and clinical history with the localization and distribution of 239-Pu in archived human skeletal samples (U.S. and Russian). To determine the influence of late chronic diseases on the redistribution of Pu among organ systems. These data may substantially alter current dosimetry and risk models. 5) Determine the tissue localization of 241-Am vs. 239-Pu. This will provide insights into the cells at risk for transformation and also more biokinetic information on 241-Am, an important byproduct of nuclear technologies. 6) Data from aims 3 and 4 with human data will be used to test human models of alpha exposure from plutonium. Gaps in the model will be filled with data from experimental studies from Aims 1,2 and 5. 7) To develop a general risk model for alpha-induced neoplasms. For this, data in human and experimental studies on radium will be used as a basis for extrapolation to other alpha-emitting nuclides.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA066759-08
Application #
6619700
Study Section
Special Emphasis Panel (ZRG1-RAD (03))
Program Officer
Pelroy, Richard
Project Start
1996-05-15
Project End
2006-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
8
Fiscal Year
2003
Total Cost
$242,320
Indirect Cost
Name
University of Utah
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Lyovkina, Yekaterina V; Miller, Scott C; Romanov, Sergey A et al. (2010) Quantitative plutonium microdistribution in bone tissue of vertebra from a Mayak worker. Health Phys 99:464-70
Lloyd, R D; Taylor, G N; Miller, S C et al. (2006) Ancestry of beagles in lifespan studies of radionuclide toxicity at the University of Utah. Health Phys 90:580-2
Luciani, A; Polig, E; Lloyd, R D et al. (2006) Americium in the beagle dog: biokinetic and dosimetric model. Health Phys 90:459-70
Lloyd, Ray D (2005) Nonmelanoma gingival malignancies and tooth loss among beagles injected with 90Sr. Health Phys 89:278-9; author reply 280
Krahenbuhl, M P; Bess, J D; Wilde, J L et al. (2005) Uncertainties analysis of doses resulting from chronic inhalation of plutonium at the Mayak production association. Health Phys 89:33-45
Lloyd, R D; Bruenger, F W; Taylor, G N et al. (2005) Search for a genetic link for mammary cancer in a beagle colony. In Vivo 19:723-7
Lloyd, Ray D; Thurman, Gary B; Taylor, Glenn N et al. (2005) Does the severity of radionuclide-induced skeletal malignancy depend upon radiation dose? Health Phys 88:491-6
Polig, E; Lloyd, R D; Bruenger, F W et al. (2004) Biokinetic model of radium in humans and beagles. Health Phys 86:42-55
Polig, E; Bruenger, F W; Lloyd, R D et al. (2004) Survival and bone tumor hazard from internal deposition of 226Ra in beagles. Health Phys 86:590-602
Lloyd, Ray D; Taylor, Glenn N; Miller, Scott C (2004) Does low dose internal radiation increase lifespan? Health Phys 86:629-32

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