1. IAEA International Atomic Energy Agency Basics of Biodosimetry Part 1 Lecture Module 2

2. IAEA What is Biodosimetry? Biodosimetry is the use of any biological change in an irradiated person that can be sufficiently quantified to indicate their radiation dose 2

3. IAEA The ideal specification for a biological dosemeter Specific to radiation Low background Low donor variability Low doubling dose Dose response calibration Persistent effect Easy sampling Rapid result Cost 3

4. IAEA What are our options? For high doses: >2 Gy Prodromal nausea and vomiting Differential white blood cell counts Localised > 3 Gy Erythema Conjunctivitis 4

5. IAEA Erythema and blistering 5

6. IAEA Changes in neutrophil numbers after irradiation % of normal Normal Time, d Infections, fever, death Critical period,infections,fever <1 2 - 5 1 - 2 >5 - 6 180 100 50 0 0 45 30 Gy 15 6

7. IAEA Other possible endpoints Altered levels of biochemicals in body fluids Gene mutations Genes up- or down-regulated Increased numbers of DNA double strand breaks 7

8. IAEA Our best options Cytogenetic indicators: Dicentrics Translocations Micronuclei Aberrations in prematurely condensed chromosomes 8

9. IAEA Why do we need biodosimetry ? Doctors treat symptoms, not doses Biodosimetry can detect false positives and false negatives Biodosimetry can forewarn to expect later clinical developments Biodosimetry can indicate partial body or inhomogeneous exposure 9

10. IAEA Why do we need biodosimetry? Dose information can inform doctors in the dose range where medical intervention is needed Doses <1 Gy will need no treatment, only counselling False alarms, i.e., no dose, need reassurance Large events result in epidemiology follow- up 10

11. IAEA Why do we need biodosimetry? Physical dosemeter badges do not necessarily reflect the wearer’s dose People, sometimes members of the public, who are not routinely monitored can be involved in radiation events 11

12. IAEA Overall place of biodosimetry in radiation dose monitoring It supplements, but does not replace, physical monitoring It works for overdoses, it does not have the sensitivity of a badge It resolves anomalies It helps quantify dose in the absence of reliable physics It relieves anxiety 12

13. IAEA Brief early history of cytogenetic dosimetry Early in the 20 th century it was known that radiation damages chromosomes 1960 breakthrough; method to visualize human chromosomes in white blood cells Calibrations at Oak Ridge, USA Biodosimetry performed on mid-1960s criticality accidents in USA 13

14. IAEA The dicentric assay The first type of aberration to be used Most frequently still used Therefore a large body of experience Now a routine procedure Has been described as the biodosimetry ‘gold standard’ 14

15. IAEA A dicentric in a metaphase chromosome spread 15

16. IAEA What is the ‘dose’ that we are measuring? Absorbed dose Unit is gray (Gy) We relate the chromosome aberration yield to dose by reference to a dose response calibration curve in Gy We are measuring dose to lymphocytes We do NOT operate in sieverts (Sv) 16

17. IAEA What are the lymphocytes that we use 17

18. IAEA Lymphocytes PHA stimulates T-lymphocytes Lymphocytes in the blood are non-dividing They are a synchronised population of cells that can be stimulated to divide and can be harvested at first metaphase In non-dividing cells dicentrics are predominantly induced by radiation 18

19. IAEA The lymphocyte in vitro cell cycle 19

20. IAEA Conclusions This lecture has described: Requirements for biological dosemeter Clinically observable effects of high doses; poorly quantitative Best options for more quantitative dosimetry; cytogenetics Why we need biodosimetry; how it helps Early beginnings in 1960s with the dicentric Consideration of dose that we specify Some basic points about peripheral blood lymphocyte 20