Dr. Antone Brooks

1

Linear-No-Threshold Hypothesis- Scientific
Evidence?

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

2
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
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
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
Problems Associated with Estimating Health Risks

• Background radiation (dose)
• Background cancer (response)

6

Normal annual exposure from man-made radiation

• 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

7
Exposure at Different Elevations
1 mrem/year 200 feet of altitude 4 mrem/year
800 feet 500 mrem/year some isolated
populations
8
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
(No Transcript)
10
Key Research Areas

• Technological Advances
• Biological Advances

11
Major Paradigm Shifts

• Hit Theory vs. Bystander Effects
• Mutation vs. gene induction
• Genomic instability vs. multiple steps in
  carcinogenesis

12
How Does Radiation Interact with Cells?

• Past
• Hit theory
• Direct ionization
• Free radical formation

• Present
• Bystander effects
• Cell-cell communication
• Cell-matrix communication

13
Schematic of the Gray Laboratory Microfocus X-ray
source
14
Microbeam
Alpha Hits for Cell Transformation
Each cell hit by one particle
Average of one particle/cell
Miller et al.1999
15
Bystander Effects
Normal
3 cGy
10 cGy
16
Biological Changes Detected in Non-hit Cells

• Gene induction
• Mutations
• Chromosome aberrations
• Apoptosis and cell killing
• Cell transformation

17
Adaptive Response Radiation-induced Chromatid
Aberrations
Aberrations
Dose cGy
Shadley and Wolff 1987
18
7K Microarray Results for Stress Chip Clone
Selection
Fornace
19
Gene Mutation and Expression in Cancer
Tissue Theory
Mutation Theory
Tissues suppress cancer.
Single cell origin of cancer
Normal
Gene Activation
Normal
Initiation
Down Regulation
Promotion
Progression
Progression
Gene Mutation- a rare event
Gene Expression- a common event
20
LNTH Assumption with Dose
Low dose x large number of subjects
High dose x small number of subjects
Energy to system
21
Absorbed Dose-Imparted Energy
Biological Response Barrier
Number Responding
Background Energy Level
Imparted Energy (J) in System
22
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

23
Adequate Protection

• Control Contamination
• Minimize Exposure
• Reduce Dose
• How low is low enough? Zero?

24
Adequate Protection
25
Adequate Protection
26
Adequate Protection
27
Adequate Protection
28
Adequate Protection
Adequate and Appropriate?
29
Questions and Problems Associated with
Dose-Response Relationships

• Ratios
• Energy/MassDose
• Damage/MassResponse
• What is the appropriate mass?
• Is there a free lunch?
• Is the biological response unique at low
  radiation doses?
• Is extrapolation possible?

30
Do New Paradigms Impact Standards?
NON-LINEAR
Gene Expression vs. Mutation
Multiple Independent Events vs. Genomic
Instability
Tissue vs. Cell
LINEAR
31
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.