VIEWS: 3 PAGES: 31 POSTED ON: 11/9/2009
Linear-No-Threshold HypothesisScientific Evidence? Dr. Antone Brooks Washington State University Tri-cities Richland, Washington 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 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 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 Problems Associated with Estimating Health Risks • Background radiation (dose) • Background cancer (response) Normal annual exposure from natural radiation 300 mrem/year Radon gas Human body Rocks, soil Cosmic rays 200 mrem 40 mrem 28 mrem 27 mrem Normal annual exposure from man-made radiation 70 mrem/yr Medical procedures Consumer products One coast to coast airplane flight Watching color TV Sleeping with another person Weapons test fallout Nuclear industry 53 mrems 10 mrems 2 mrems 1 mrem 1 mrem less that 1 mrem less than 1 mrem Exposure at Different Elevations 140 120 100 80 60 40 20 0 mrem / year Sea Level Death Valley Richland Denver Ledville 1 mrem/year = 200 feet of altitude 4 mrem/year = 800 feet 500 mrem/year = some isolated populations 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 Key Research Areas • Technological Advances • Biological Advances Major Paradigm Shifts • Hit Theory vs. Bystander Effects • Mutation vs. gene induction • Genomic instability vs. multiple steps in carcinogenesis How Does Radiation Interact with Cells? Past Hit theory • Direct ionization Present Bystander effects • Cell-cell communication • Free radical formation • Cell-matrix communication Microbeam Alpha Hits for Cell Transformation Each cell hit by one particle Average of one particle/cell Miller et al.1999 Bystander Effects Normal 3 cGy 10 cGy Biological Changes Detected in Non-hit Cells • Gene induction • Mutations • Chromosome aberrations • Apoptosis and cell killing • Cell transformation Adaptive Response Radiation-induced Chromatid Aberrations 90 80 70 60 50 40 30 20 10 0 0 0.5 1 150 150 + .5 150 + 1 Observed Expected Dose cGy Shadley and Wolff 1987 7K Microarray Results for “Stress Chip” Clone Selection Dose (Gy) Time (Hr) Induced Repressed Genes Genes 2.5 0.2 .02 24 24 24 62 114 55 8 11 6 Fornace Gene Mutation and Expression in Cancer Single cell origin of cancer Normal Gene Activation Normal Initiation Promotion Progression Gene Mutation- a rare event Down Regulation Progression Gene Expression- a common event LNTH Assumption with Dose High dose x small number of subjects Energy to system Low dose x large number of subjects Absorbed Dose-Imparted Energy Biological Response Barrier B A B Background Energy Level Imparted Energy (J) in System 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 Adequate Protection • Control Contamination • Minimize Exposure • Reduce Dose How low is low enough? “Zero”? Adequate Protection Adequate Protection Adequate Protection Adequate Protection Adequate Protection Adequate and Appropriate? 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? Do New Paradigms Impact Standards? NON-LINEAR Tissue Multiple Independent Events Gene Expression vs. Cell vs. Genomic Instability vs. Mutation LINEAR 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.
Pages to are hidden for
"Overview of Basic Radiation Biology"Please download to view full document