Notion de base de radioprotection RPR 2001 - UCLouvain · dosimétrie des travailleurs; visites des installations du contrôle physique Plan du cours Prof. V. Grégoire ... Cours_RPR_2001_1

Notion de base deNotion de base de radioprotectionradioprotectionRPR 2001RPR 2001

Prof. V. GREGOIREDr. P. SMEESTERS

1. Grandeurs et Unités - Mécanismes biologiques de l’action des rayonnements ionisants

2. Effets aigus d ’une irradiation accidentelle3. Cancers radio-induits4. Effets héréditaires radio-induits5. Effets de l ’irradiation in utero6. Législation: les normes de bases; principes de radioprotection

opérationnelle7. Travaux pratiques: emploi de détecteurs en situation de routine;

dosimétrie des travailleurs; visites des installations du contrôlephysique

Plan duPlan du courscours

Prof. V. GrégoireDr. P. SmeestersProf. A. Wambersie, Mr J. Caussin

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• Radiobiology for the Radiologist, Eric J. Hall. J.B.Lippincott Company, Philadelphia, 1994.

• 1990 recommendations of the International Commission on Radiological Protection, Annals of the ICRP, publication 60, 1991.

• Exposure to ionizing radiations: radiobiological effects and pathogenesis, A. Wambersie et al., Revue Médicale de Bruxelles, 17: 27-38 et 75-84, 1996 ou Louvain Med., 114: S97-S132, 1995.

• http://www.md.ucl.ac.be/rbnt/RPR2001.htm

OuvragesOuvrages dede référenceréférence

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• Electromagnetic radiation (low LET): photons, γ-rays, X-rays

• Particulate Radiation(high LET)

- charged particles: electrons, protons, α particles- neutrons- heavy charged ions: carbon, neons, argon, …

Types of ionizing radiationTypes of ionizing radiation

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Electromagnetic radiationElectromagnetic radiation

E = hν

ν = c/λ

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• Indirectly ionizing radiation: X-rays, γ-rays, neutrons- photoelectric process: ˜ Z3

- Compton process: higher photon energy- pair production

• Directly ionizing radiation: charged particles

Absorption of XAbsorption of X--raysrays

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Absorption of XAbsorption of X--raysraysCompton processCompton process

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Absorption of XAbsorption of X--raysraysPhotoelectric processPhotoelectric process

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Absorption of XAbsorption of X--raysraysPair productionPair production

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Absorption of XAbsorption of X--raysraysDirect and indirect actionDirect and indirect action

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Absorption of XAbsorption of X--raysraysRadiolysis Radiolysis of waterof water

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Absorption of neutronsAbsorption of neutrons

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The physics and chemistry of The physics and chemistry of radiation absorptionradiation absorption

Low and high LET radiationLow and high LET radiation

Low LET High LET

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DepthDepth--dose curvesdose curves

Electrons Photons

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Chronology of eventsChronology of events

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The physics and chemistry of radiation The physics and chemistry of radiation absorptionabsorption

TakeTake--home messagehome message

• X- and γ-rays are indirectly ionizing; the first step in their absorption is the production of fast recoil electrons.

• Neutrons are also indirectly ionizing; the first step in their absorption is the production of fast recoil protons, α-particles, and heavier nuclear fragments.

• Electrons and other charged particles are directly ionizing; they lost their energy by progressive collision.

• The shape of the depth-dose curves (and thus the absorption) depends on the type of ionizing radiation and their energy.

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The physics and chemistry of radiation The physics and chemistry of radiation absorptionabsorption

TakeTake--home messagehome message

• Biological effects of X-rays may be due to the direct or indirect action

• About two thirds of the biological damage by X-rays is due to indirect action

• High-LET radiations produce most biological damage by the direct action, which cannot be modified by chemical sensitizers and protectors

• The physics of the absorption process is over 10-15 second; the chemistry takes longer; the biology takes days to months for cell killings, years for carcinogenesis, and generations for heritable damage

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Quantities and unitsQuantities and unitsAbsorbed dose: 1 Gray (Gy) = 1 joule/kg

= increase of 0.0001 °C per gr water

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Quantities and unitsQuantities and units

Equivalent dose = absorbed dose * radiation weighting factor (WR)

in Sievert (Sv)

Type and energy range WR

Photons, all energies 1Electrons, all energies 1Neutrons, < 10 keV 5

> 10 keV < 100 keV 10> 100 keV < 2 MeV 20> 2 MeV < 20 MeV 10> 20 MeV 5

Protons, > 2 MeV 5α-particles, fission fragments, heavy nuclei 20From ICRP 60

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Quantities and unitsQuantities and unitsEffective dose = Σ absorbed dose * WR * tissue weighting factor (WT)

in Sievert (Sv)

Tissue or organ WT

Gonads 0.20Bone Marrow 0.12Colon 0.12Lung 0.12Stomach 0.12Bladder 0.05Breast 0.05Liver 0.05Esophagus 0.05Thyroid 0.05Skin 0.01Bone surface 0.01Remainder 0.05

From ICRP 60

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Committed equivalent dose = equivalent dose over 50 years (70 years for children)

Committed effective dose = effective dose over 50 years (70 years for children)

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Collective equivalent dose = equivalent dose * number of persons exposed (in person-Sievert)

Collective effective dose = effective dose * number of persons exposed (in person-Sievert)

Collective effective dose commitment = committed effective dose *number of persons exposed (in person-Sievert)

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Quantities and unitsQuantities and unitsTakeTake--home messagehome message

• For individuals- absorbed dose- equivalent dose- effective dose- committed equivalent dose- committed effective dose

• For populations- collective equivalent dose- collective effective dose- collective effective dose commitment

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Digest in Radiation BiologyDigest in Radiation BiologyCellular processes involved in

cell death after ionizing radiations.

Free-radical production Direct effect

Initial genomic damage(DNA / chromosome)

Residual genomic damage(DNA / chromosome)

Clonogenic cell death

Ionizations / Excitations

Programmed cell death

Tumor shrinkage Loss of normal tissue functionalIntegrity including carcinogenesis

Repair processes Division delay

Cell surfacereceptor

Signal transductionpathways

Ionizing radiations

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Digest in Radiation BiologyDigest in Radiation BiologyClonogenic cell survival.

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Digest in Radiation BiologyDigest in Radiation BiologyTime-lapse microcinematography

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From Schwartz et al.

10 -3

10 -2

10 -1

10 0

0 2 4 6 8 10 12 14

SCC 61 SCC 12 B2

Absorbed dose (Gy)

Surv

ivin

g fr

actio

n

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Digest in Radiation BiologyDigest in Radiation BiologyThe key function of DNA

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Digest in Radiation BiologyDigest in Radiation BiologyStructure of DNA

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Digest in Radiation BiologyDigest in Radiation BiologyStructure of DNA

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Digest in Radiation BiologyDigest in Radiation BiologyDNA damages

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Digest in Radiation BiologyDigest in Radiation BiologyDNA damages

Type of lesion Number per Gray

Double strand breaks (dsb) 40

Single strand breaks (ssb) 500-1000

Base damage 1000-2000

Sugar damage 800-1600

DNA-DNA crosslinks 30

DNA-protein crosslinks (dpc) 150

Alkali-labile sites 200-300

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Digest in Radiation BiologyDigest in Radiation BiologyQuantification of DNA damages

0

0.1

0.2

0.3

0.4

0.5

0 10 20 30 40

Frac

tion

of a

ctiv

ity re

leas

ed

Absorbed dose (Gy)

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Digest in Radiation BiologyDigest in Radiation BiologyDNA Repair

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Digest in Radiation BiologyDigest in Radiation BiologyDNA Repair

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Digest in Radiation BiologyDigest in Radiation BiologyQuantification of DNA Repair

Repair time (min.)0 60 120 180 240 300 360

100

10

HF19

180BRPe

rcen

t of i

nitia

l dam

age

From Badie et al.

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Digest in Radiation BiologyDigest in Radiation BiologyStructure of chromosome

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Digest in Radiation BiologyDigest in Radiation BiologyChromosome and chromatid aberrations

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Digest in Radiation BiologyDigest in Radiation BiologyChromosome aberrations

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Digest in Radiation BiologyDigest in Radiation BiologyQuantification of chromosome breaks

From Hittelman et al.

0

10

20

30

40

50

60

0 1 2 3 4 5 6

SCC 61

SCC12 B2

Absorbed dose (Gy)

Chr

omos

ome

brea

ks p

er c

ell

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Digest in Radiation BiologyDigest in Radiation BiologyQuantification of chromosome dicentrics and rings

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Digest in Radiation BiologyDigest in Radiation BiologyOverview of the cell cycle

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Digest in Radiation BiologyDigest in Radiation BiologyCell cycle control: G1-S transition

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Digest in Radiation BiologyDigest in Radiation BiologyTumor suppressor gene: the retinoblastoma example

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Digest in Radiation BiologyDigest in Radiation BiologyProgrammed cell death - apoptosis >< necrosis

phagocytose

APOPTOSE

NECROSE

inflammation

gonflement cellulaire,lésion des organites,altération de la chromatine.

lyse cellulaire,destruction des organites,destruction de la chromatine.

condensation de la chromatine,diminution du volume cellulaire,changements membranaires.

chromatine fragmentée,organites intacts.

formation des corps apoptotiques

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Digest in Radiation BiologyDigest in Radiation BiologyProgrammed cell death - apoptosis

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Digest in Radiation BiologyDigest in Radiation BiologyProgrammed cell death - apoptosis: an active process

FasL,TNFα

privation en facteursde croissance perforine

granzyme Bautres

1° signal

3° exécution

Bcl-2, Bcl-xLmitochondrie mitochondrie

caspases

CrmAp35

ZVADYVADDEVD

ψm, cytochrome cAIF, radicaux libres

Apoptose

boucle d ’auto-amplification

2° contrôle

point denon retour

stress oxidatifradiations ionisanteslésions à l’ADN (p53)

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Digest in Radiation BiologyDigest in Radiation BiologyProgrammed cell death - apoptosis: DNA fragmentation

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Digest in Radiation BiologyDigest in Radiation BiologyThe p53-dependant signaling pathways

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Digest in Radiation BiologyDigest in Radiation BiologyThe p53-dependant signaling pathways

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Digest in Radiation BiologyDigest in Radiation BiologyHypersensitivity syndromes

Deschavanne & Malaise, 1986

Mean inactivating dose (Gy)

AT+ +

AT+ - FA

Nl.99

.9

.7

.5

.2

.1

.010 0.5 1 1.5 2 2 .5 3

Cum

ulat

ive

freq

uenc

y

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Digest in Radiation BiologyDigest in Radiation BiologyRelative Biological Effectiveness (RBE)

High LET

Low LETSu

rviv

ing

frac

tion

Dose (Gy)

RBE = Dlow LET / Dhigh LET

Dhigh LET Dlow LET

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Digest in Radiation BiologyDigest in Radiation BiologyRBE and LET

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Digest in Radiation BiologyDigest in Radiation BiologyTakeTake--home message 1.home message 1.

• Many single-strand damages are produced in DNA by radiation but are readily and faithfully repaired using the opposite DNA strand as a template.

• Damages in both strands that are opposite, separated by only a few base pairs, or locally multiple may lead to a double-strand break (dsb).

• In mammalian cells, double-strand breaks are mainly repaired by non-homologous end joining (NHEJ).

• Damages that are not repaired or that are mis-repaired in pre-replication phase (G0-G1 cells) may lead to chromosome aberrations.

• Damages that are not repaired or that are mis-repaired in post-replication phase (late-S or G2 cells) may lead to chromatid aberrations.

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• Asymetrical exchange aberrations (dicentrics and rings) are mainly lethal.

• Symetrical exchange aberrations (translocations and deletions) resulting frommis-repaired DNA damages may lead to carcinogenesis.

• Techniques available to study DNA dsbs are not sensitive enough to be used as biological dosimetry in case of accidental irradiation.

• Scoring aberrations in lymphocytes from peripheral blood may be used to estimate total-body doses in humans with a sensitivity of ˜ 0,25 Gy.

• Ionizing radiation induce a cell cycle arrest at the G1-S border to prevent damaged DNA to be replicated in S-phase.

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• �After exposure to ionizing radiation, cells mainly die from necrosis(clonogenic cell death).

• Apoptosis is an “active” form of cell death which is involved in tissue homeostasis after ionizing radiation (e.g. preventing carcinogenesis).

• Genetic predisposition (e.g. mutations in p53, Rb, or AT gene) may render cells more sensitive to ionizing radiations.

• Hight LET radiations (e.g. neutrons, α-particles) are much more effective than X-rays or γ-rays (RBE > 1).

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Notion de base de radioprotection RPR 2001 - UCLouvain · dosimétrie des travailleurs; visites des installations du contrôle physique Plan du cours Prof. V. Grégoire ... Cours_RPR_2001_1