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

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Page 1: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

IAEAInternational Atomic Energy Agency

Basics of BiodosimetryPart 1

LectureModule 2

Page 2: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

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

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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

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IAEA

What are our options?

For high doses:>2 GyProdromal nausea and vomitingDifferential white blood cell counts

Localised > 3 GyErythemaConjunctivitis

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IAEA

Erythema and blistering

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IAEA

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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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

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Page 8: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

IAEA

Our best options

Cytogenetic indicators:

• Dicentrics• Translocations• Micronuclei• Aberrations in prematurely condensed

chromosomes

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Page 9: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

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

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Page 10: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

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

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Page 11: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

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

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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

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Page 13: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

IAEA

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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Page 15: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

IAEA

A dicentric in a metaphase chromosome spread

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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)

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IAEA

What are the lymphocytes that we use

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Page 18: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

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

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Page 19: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

IAEA

The lymphocyte in vitro cell cycle

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Page 20: [PPT]PowerPoint Presentation · Web view‘Phytohaemagglutinin: an initiator of mitosis in cultures of normal human leukocytes’. ... harvest the metaphases and place them on slides

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

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