1 / 37

Health Effects of Alpha Emitters (Mechanistic Basis)

Health Effects of Alpha Emitters (Mechanistic Basis) Antone L. Brooks Washington State University Tri-Cities Health Physics Society Spokane WA July 10-14, 2005 Past Assumptions About Exposure to Alpha Emitters Hit cell has large radiation dose and effect

issac
Download Presentation

Health Effects of Alpha Emitters (Mechanistic Basis)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Health Effects of Alpha Emitters (Mechanistic Basis) Antone L. BrooksWashington State University Tri-Cities Health Physics SocietySpokane WA July 10-14, 2005

  2. Past Assumptions About Exposure to Alpha Emitters • Hit cell has large radiation dose and effect • Hit cells killed mutated and transformed as a function of hit number • No dose-rate effect for exposure to alpha emitters. • Linear-no-threshold dose-response for many biological endpoints including cancer.

  3. Health Effects from Alpha Emitting Radioactive Material • Radium dial painters • Thorotrast patients • Uranium miners • Workers in the production of Nuclear Weapons

  4. 70 60 50 Percent tumor cumulative incidence 40 30 20 10 10 100 1000 10000 100000 Dose Response For human cancer Bone sarcoma in Radium dial painters Evans 1981

  5. Induction of Liver Cancer from Thorotrast Injection 50Gy 40Gy 10Gy NCRP Report 135

  6. Relative Risks calculated from: Indoor studies (case control) Miner studies (cohort) 5 1 0.3 0 100 200 300 400 Radon-induced lung cancer Relative Risk Relative Risk=1 Radon Concentration (Bq/m3) BEIR VI

  7. Distribution of Attributable Risk(BEIR VI Model) Exposure (Bq/m3) % Homes AR 0-150 94.3 70% 150-600+ 5.7 30%

  8. How do Animal studies Help? • Little information available on many of the alpha emitting isotopes (239Pu, 241Am, 238Pu) • Lifespan dose-response studies help link to human data • Address specific problems like influence of dose distribution, age or dose patterns. • Ya, but what if? “Hot Particle Hypothesis”.

  9. Hot Particle Hypothesis • Cellular dose and response are linked • Non-uniform dose distribution results in increased risks • Large doses to a few cells result in large risks • Hypothesis suggests that risk from inhaled plutonium particles too low by a factor of 100,000-200,000. • Studies demonstrated that this was false.

  10. Non-Uniform Dose Distribution from Plutonium Inhalation

  11. The Influence of 239PuO2 Particle Size on the Dose-Distribution in the Liver of Chinese Hamsters Citrate 0.44µm 0.84µm 0.17µm

  12. The Influence of 239Pu Dose-Distribution on Chromosome Aberration Frequency Aberrations/Cell Brooks et al

  13. Influence of dose distribution on risk • There is no evidence that organs outside of the target organ are at increased risk from the internal emitter. • For tissue, the more uniform the distribution of dose, the higher the risk. • For cells, the more cells that are hit, the higher the risk. • Concentrated “hot spots” produce less risk of cancer than uniform dose-distribution.

  14. Biological parameters that influence responses from Alpha emitters • Biological endpoint • Species • Genetic background and repair capability • Tissue and organ type

  15. Radon- induced lung cancer in rats Nasal + Trachea 0 Deep lung fibroblasts + Deep lung epithelial cells ++++

  16. 32.8 + 2.4 Tracheal epithelial cells ? 76.2 + 7.9 Deep lung fibroblasts 92.2 + 9.2 Deep lung epithelial cells 34.5 + 4.3 Nasal epithelium Radon in RatsInduction of micronuclei(micronuclei/1000 cells/Gy

  17. Relationships between insults using Cellular Biodosimetry Alpha Hits/ dose (mGy) Alpha Hits/exposure (WL) Dose (mGy)/exposure (WL)

  18. Key Research Areas • Technological Advances • Biological Advances

  19. Key Research Areas Technological Advances

  20. Viewing Light Scintillation Detector Scintillation Plastic Piezoelectric Shutter Manually Adjustable Collimeter Faraday Cup Beam Control Slits Beam from Accelerator Vertical Bending Magnet Alpha-Particle Radiation System Video Camera Microscope Objective Lens Newport Positioning Stage Mylar Bottom Petri Dish Texas A&M

  21. Microbeam Hit Accuracy

  22. Selection of Target • Cell • Nucleus • Cytoplasm

  23. Control Distribution of Energy • Distribution of energy • Distribution of damage

  24. Key Research Areas Biological Advances

  25. Cellular Changes • Adaptive Response • Small dose alters response to large dose • Small dose decreases spontaneous damage • Bystander Effects • Cells respond without energy deposition • Cell-cell communication • Materials into the media • Genomic Instability • Loss of genetic control many cell generations after the radiation exposure

  26. Relationship between biological responses to radiation AdaptiveResponse Genomic Instability Bystander Effects

  27. Bystander Effects in vitro

  28. Microbeam 10 % of cells hit with 1 alpha particles Each cell hit by one particle Sawant et al. 2000

  29. Cell Transformation Sawant et al.2000

  30. Relationship between biological responses to radiation AdaptiveResponse Genomic Instability Bystander Effects

  31. Adaptive Response and alpha particles. • Low-LET radiation produces marked adaptive responses at low total doses. • Low-LET radiation results in a decrease in risk at low doses relative to that predicted by the LNTH. • Low doses of low-LET produce an adaptive response seen in bystander cells following high-LET radiation. • There is little evidence for alteration of dose-response by adaptive mechanisms following high-LET radiation.

  32. Relationship between biological responses to radiation AdaptiveResponse Genomic Instability Bystander Effects

  33. Radiation-induced Genetic Damage Old Paradigm After a cell is mutated by radiation, all of its prodigy are mutated Mutation is a rare event

  34. Micronuclei Cell death Gene mutation Mitotic failure-aneuploidy Chromosome aberration Genomic Instability New Paradigm After a cell is exposed to radiation, different things can happen …sometimes after many cell divisions. This is a frequent event.

  35. Radiation-induced Genomic Instability • High frequency event • 3%/Sv low LET • 4%/Sv high LET • Independent of dose rate at high total dose • Related to inflammation and the Redox status of the cell • Produced both in vitro and in vivo

  36. Summary • Internally deposited alpha emitting radioactive materials are more effective in producing cellular changes and cancer than low-LET radiation. • There are many alpha induced non-linear dose-response relationships for cellular changes and cancer. • Extensive evidence exists for changes in biological mechanisms as a function of dose. • These mechanisms support non-linear dose-response functions.

  37. Adaptive Response High-LET exposure Bystander Acute Low-LET exposure Direct Effects Bystander and direct effects Biological paradigm for dose-response relationships Chromosome Aberrations Background 0 20 40 60 80 Dose (cGy)

More Related