1. DNA Damage and Biodosimetry
Radiation, through free radical formation, causes damage to DNA
Cells have very efficient DNA repair mechanisms (argues against LNT hypothesis)
Damage to DNA/chromosomes from radiation can be measured to determine amount of radiation exposure.

2. Types of DNA repair: Damage on/to single strands
Incorrect base due to
Spontaneous reactions
Base analogs
Copying errors
Breaks in a DNA strand due to radiation
Excision repair:
Section of DNA with error cut out
Enzyme puts in new DNA using complementary strand
Rejoining of broken strand

3. Types of DNA repair: Double strand breaks
Homologous repair
DNA has been copied, so sister chromatid is available.
Recombination event uses same (or similar DNA)
May result in wrong section being used: mutation.
Non-homologous end-rejoining
Ends just stitched back together

4. saturn.roswellpark.org/.../ DNA_Repair/SSBR.gif

5. Failure to repair Damaged DNA has consequences
Senesence: cell stops dividing when it should continue
Apoptosis: damaged DNA stimulates programmed cell death
Carcinogenesis: damage DNA interferes with cell regulation, cells divide out of control.

7. Deinococcus radiodurans
Gram positive bacterium
Apparently fairly ancient
High resistance to radiation damage
Why? Earth never that radioactive.
Highly efficient DNA repair
Adapted to resist dessiccation, oxidation damage to DNA
Multiple copies of genes for DNA repair enzymes

8. Chromosomal aberrations
Deletions, rings, dicentrics
Micronuclei: chromosome fragments

9. Translocations Chromosomes swab pieces DNA breaks, attaches elsewhere

10. Biodosimetry: use of chromosomal change to estimate radiation dose
Chromosomal aberrations
Effective range: rem exposure
Time from dosage must be considered due to repair
1000 hits occur and repaired before one seen
Repair is continual, so #s decrease over time
Dicentrics most commonly used
Most dicentric chromosomes are radiation induced
Micronuclei
From as low as 1 rem exposure; recent exposures only.

12. Translocations Not readily repaired (caused by ds break repair)
Not readily repaired (caused by ds break repair)
Good for estimating lifetime dose
Background rate: 1-4 translocations per 1000 cells

13. Radiation Protection Dosimetry 88:77-86 (2000) © 2000 Oxford University Press
Our Views on Issues in Radiation Biodosimetry Based on Chromosome Translocations Measured by FISH
J.N. Lucas and W. Deng
A biomarker for retrospective biodosimetry for radiation exposure and human health risk assessment would be most useful if it employed an endpoint that is highly quantitative, is stable over time, and is relevant to human health risk. The frequency of chromosome translocations in individuals exposed to low to medium doses of whole-body radiation serves these goals. Recent advances in chromosome painting using fluorescence in situ hybridisation (FISH) facilitate fast and reliable measurement of chromosome translocations, a kind of DNA damage linked to both prior clastogenic exposure and to human health risk.

14. Using FISH to spot translocations

15. Current trends in biodosimetry
Molecular biomarkers for ionizing radiation exposure (gene expression changes, blood proteins) can be measured in real time using such diagnostic detection technologies as miniaturized nucleic acid sequences and antigen-based biosensors
Certain genes are turned off or on by acute radiation exposure; RT-PCR to detect, quantify.
Examination of biological tissue (e.g. teeth) using EPR (electron paramagnetic resonance)
Ionization affects electron spin changes

16. Follow the money
After a large-scale radiological event, there would be a major need to assess, within a few days, the radiation doses received by tens of thousands of individuals. By contrast, current “high throughput” biodosimetry can, at best, assess a few hundred individuals / day. The Center for High-Throughput Minimally-Invasive Radiation Biodosimetry is a research consortium devoted to developing high-throughput radiation dose assessment techniques.