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

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

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

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

IAEAInternational Atomic Energy Agency

Basics of BiodosimetryPart 1

LectureModule 2

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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

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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

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What are our options?

For high doses:

>2 Gy

Prodromal nausea and vomiting

Differential white blood cell counts

Localised > 3 Gy

Erythema

Conjunctivitis

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Erythema and blistering

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Changes in neutrophil numbers after irradiation

% ofnormal

Normal

Time, d

Infections, fever, death

Critical period,infections,fever

<1

2 - 51 - 2

>5 - 6

180

100

50

00 4530

Gy

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Other possible endpoints

• Altered levels of biochemicals in body fluids

• Gene mutations

• Genes up- or down-regulated

• Increased numbers of DNA double strand breaks

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Our best options

Cytogenetic indicators:

• Dicentrics

• Translocations

• Micronuclei

• Aberrations in prematurely condensed chromosomes

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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

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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

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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

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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

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Brief early history of cytogenetic dosimetry

• Early in the 20th 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

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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’

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A dicentric in a metaphase chromosome spread

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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)

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What are the lymphocytes that we use

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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

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The lymphocyte in vitro cell cycle

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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

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