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Dr. Antone Brooks Washington State University Tri-cities Richland, Washington

Biological and Environmental Research. Low Dose Radiation Research Program. Linear-No-Threshold Hypothesis- Scientific Evidence?. Dr. Antone Brooks Washington State University Tri-cities Richland, Washington. Biological and Environmental Research. Low Dose Radiation Research Program.

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Dr. Antone Brooks Washington State University Tri-cities Richland, Washington

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  1. Biological and Environmental Research Low Dose Radiation Research Program Linear-No-Threshold Hypothesis- Scientific Evidence? Dr. Antone Brooks Washington State University Tri-cities Richland, Washington

  2. Biological and Environmental Research Low Dose Radiation Research Program My Background • Early interest in radiation (Watching atomic weapons in southern Utah) • MS in radiation ecology (Chasing fallout) • PhD in radiation biology in genetics (Trying to discover what radiation is actually doing inside people) • Investment of my life in research on health effects of low doses of radiation

  3. Biological and Environmental Research Low Dose Radiation Research Program DOE Low-Dose Radiation Research Program • A 10 year program at $21 million/year • International in scope • To fund the best scientist (currently 46 projects/year) • To understand biological mechanisms • To develop radiation standards based on risk http://lowdose.org

  4. Biological and Environmental Research Low Dose Radiation Research Program Why now? • Standards have been set from high dose effects, but low dose effects have not been measurable until now • New technological developments and biological discoveries have made it possible to study low dose effects

  5. Biological and Environmental Research Low Dose Radiation Research Program Problems Associated with Estimating Health Risks • Background radiation (dose) • Background cancer (response)

  6. Normal annual exposure from natural radiation 300 mrem/year • Radon gas 200 mrem • Human body 40 mrem • Rocks, soil 28 mrem • Cosmic rays 27 mrem 70 mrem/yr • Medical procedures 53 mrems • Consumer products 10 mrems • One coast to coast airplane flight 2 mrems • Watching color TV 1 mrem • Sleeping with another person 1 mrem • Weapons test fallout less that 1 mrem • Nuclear industry less than 1 mrem Normal annual exposure from man-made radiation

  7. Exposure at Different Elevations 1 mrem/year = 200 feet of altitude 4 mrem/year = 800 feet 500 mrem/year = some isolated populations

  8. Biological and Environmental Research Low Dose Radiation Research Program Background Cancer Over 30 % of us will develop cancer About 25 % will die of cancer Cancer is variable as a function of • Genetic Background • Environmental Exposures • Diet • Lifestyle

  9. Biological and Environmental Research Low Dose Radiation Research Program Key Research Areas • Technological Advances • Biological Advances

  10. Biological and Environmental Research Low Dose Radiation Research Program Major Paradigm Shifts • Hit Theory vs. Bystander Effects • Mutation vs. gene induction • Genomic instability vs. multiple steps in carcinogenesis

  11. Past Hit theory Direct ionization Free radical formation Present Bystander effects Cell-cell communication Cell-matrix communication How Does Radiation Interact with Cells?

  12. Schematic of the Gray Laboratory Microfocus X-ray source

  13. Biological and Environmental Research Low Dose Radiation Research Program Microbeam Alpha Hits for Cell Transformation Each cell hit by one particle Average of one particle/cell Miller et al.1999

  14. Biological and Environmental Research Low Dose Radiation Research Program Bystander Effects Normal 3 cGy 10 cGy

  15. Biological and Environmental Research Low Dose Radiation Research Program Biological Changes Detected in Non-hit Cells • Gene induction • Mutations • Chromosome aberrations • Apoptosis and cell killing • Cell transformation

  16. Biological and Environmental Research Low Dose Radiation Research Program Adaptive ResponseRadiation-induced Chromatid Aberrations Aberrations Dose cGy Shadley and Wolff 1987

  17. 7K Microarray Results for “Stress Chip” Clone Selection Fornace

  18. Gene Mutation and Expression in Cancer Tissue Theory MutationTheory Single cell origin of cancer Tissues suppress cancer. Normal Gene Activation Normal Initiation Down Regulation Promotion Progression Progression Gene Mutation- a rare event Gene Expression- a common event

  19. LNTH Assumption with Dose Low dose x large number of subjects High dose x small number of subjects Energy to system

  20. B A B Absorbed Dose-Imparted Energy Biological Response Barrier Number Responding Background Energy Level Imparted Energy (J) in System

  21. Biological and Environmental Research Low Dose Radiation Research Program Low-Dose Research Program Goals Understand mechanisms of biological response to low-dose radiation on a cellular and molecular level Evaluate appropriate and adequate risk from low doses and dose-rates of radiation

  22. Biological and Environmental Research Low Dose Radiation Research Program Adequate Protection • Control Contamination • Minimize Exposure • Reduce Dose How low is low enough? “Zero”?

  23. Biological and Environmental Research Low Dose Radiation Research Program Adequate Protection

  24. Biological and Environmental Research Low Dose Radiation Research Program Adequate Protection

  25. Biological and Environmental Research Low Dose Radiation Research Program Adequate Protection

  26. Biological and Environmental Research Low Dose Radiation Research Program Adequate Protection

  27. Biological and Environmental Research Low Dose Radiation Research Program Adequate Protection Adequate and Appropriate?

  28. Questions and Problems Associated with Dose-Response Relationships • Ratios: Energy/Mass=Dose Damage/Mass=Response • What is the appropriate mass? • Is there a “free lunch”? • Is the biological response unique at low radiation doses? • Is extrapolation possible?

  29. Do New Paradigms Impact Standards? NON-LINEAR Gene Expression vs. Mutation Tissue vs. Cell Multiple Independent Events vs. Genomic Instability LINEAR

  30. Biological and Environmental Research Low Dose Radiation Research Program Summary • Radiation risks from low levels of radiation exposure cannot be predicted with epidemiological studies. • Combining advances in technology with those in cell and molecular biology make it possible to detect biological changes after low levels of radiation exposure. • These low level changes have required changes in basic radiation paradigms. • Understanding the role of these biological changes in cancer risk may or may not impact radiation protection standards, but will help ensure that the standards are both adequate and appropriate.

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