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IAEA Training Course: Radiation Protection i n Radiotherapy slide 1 EFECTELE RADIAŢIILOR EFECTELE RADIAŢIILOR IONIZANTE IONIZANTE TIMP – imediate TIMP – imediate - tardive - tardive PERSOANA AFECTATĂ PERSOANA AFECTATĂ - somatice - somatice - la - la descendenţi descendenţi

E. Efecte Biologice

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  • EFECTELE RADIAIILOR IONIZANTETIMP imediate

    - tardivePERSOANA AFECTAT

    - somatice - la descendeni

    IAEA Training Course: Radiation Protection in Radiotherapy

  • DOZE MARI:EFECTE DETERMINISTICEDOZE MICI:EFECTE STOCASTICE

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Efecte deterministiceSe datoreaz morii celulelorAu o doza-prag de cativa GraySunt specifice in funcie de esutul afectatSeveritatea efectului este dependenta de doza

    Deterministic effects are for example:skin reddening (erythema)skin breakdown (desquamation)cataracts in the lens of the eyetumor cell killdeath

  • Efecte stocasticeSe datoreaz modificrilor celulare (ADN) si proliferrii spre boli maligneSeveritatea este independenta de dozaNu exista doza-prag:

    efectele pot sa apar si la doze foarte miciProbabilitatea de apariie a efectului creste cu doza

    dozaProbabilitatea efectului

    The major stochastic effect is cancer induction - however, also many hereditary effects are stochastic. The risk of having a malformation in a baby increases with dose- the severity of the event though is independent of it.

  • 1. Efectele radiaiilorRadiatiile ionizante interactioneaza la nivel celular prin: ionizare modificari chimice efecte biologice

    celulenucleucromozomi

    Radiatiaincidenta

    IAEA Training Course: Radiation Protection in Radiotherapy

    The lecturer can again point out the stochastic nature of the energy deposition on the scale of dimensions of a cell. In particular at low doses there may or may not be an interaction in a given nucleus. The last slide of the dosimetry lecture is repeated as next slide - hidden. The lecturer can unhide it if deemed appropriate.

  • MECANISME DE ACIUNEACIUNE DIRECT

    afectare direct a ADNACIUNE INDIRECT

    afectarea moleculelor din preajma AND i producerea de radicali liberi

    IAEA Training Course: Radiation Protection in Radiotherapy

  • MECANISME GENERALE DE ACIUNE LA NIVEL MOLECULAR

    ACIUNE PE

    MACROMOLECULE = Efect direct

    Responsabil 20% de producerea leziunilor

    IAEA Training Course: Radiation Protection in Radiotherapy

  • MECANISME GENERALE DE ACIUNE LA NIVEL MOLECULAR

    ACIUNE ASUPRA APEI

    = Efect indirectRADIOLIZA APEIRadicali liberiMacromolecule Responsabil 80% de producerea leziunilor

    IAEA Training Course: Radiation Protection in Radiotherapy

  • inta la nivelul celular: ADN

    IAEA Training Course: Radiation Protection in RadiotherapyThe discussion on how much each of the two effects - indirect and direct damage to DNA contribute to cell kill is still ongoing. In practice both play a role.

  • EFECTELE RADIAIILOR IONIZANTE

    PARTICULE NCRCATE

    INTERACIUNI ELECTRICE

    APAR IONIZRI

    MODIFICRI CHIMICE

    EFECTE BIOLOGICE

    PARTICULE NCRCATE

    INTERACIUNI ELECTRICE

    APAR IONIZRI

    MODIFICRI CHIMICE

    EFECTE BIOLOGICE

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Procese ce determina efectele StadiuProcesDurataFizice Absorptie de energie, ionizare 10-15 sFizico-chimiceInteraciunea ionilor cu moleculele, 10-6 sformarea de radicali liberiChimiceInteraciunea radicalilor liberi cu secundemoleculele, celulele si ADNBiologiceMoarte celulara, modificri genetice, zeci de minute mutaii pana la zeci de ani

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Clasificarea efectelor se face dupa modul de evolutie 1. Non-letale = mentinerea capacitatii de reproducere, dar cu crestere incetinita2. Sub-letale = supravietiurea celulei cu capacitate normala de reproducere, dupa un timp de reparare a modificarilor3. Potential letale = posibilitatea de supravietuire, cu capacitate de reproducere dupa un timp de reparare a modificarilor4. Letale = pierderea capacitatii reproductive.

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Primele observaii privind efectele radiaiilor1895 Roentgen descoper razele X1896 Se raporteaz primele arsuri radiologice1896 Se folosesc pentru prima oara radiaiile X in tratamentul cancerului1896 Becquerel descoper radioactivitatea1897 Se raporteaz primele cazuri de afeciuni cutanate1902 Prima raportare de cancer radio-indus1911 Primele raportri de leucemie si cancer pulmonar prin expunere profesionala la radiaii ionizante1911 Se raporteaz in Germania 94 de cazuri cu tumori (50 fiind radiologi)

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Monumentul pionierilor in folosirea radiaiilor ionizante care au murit datorita expunerii

    IAEA Training Course: Radiation Protection in RadiotherapyThe lecturer should point out that this was not necessarily bad practice - radiation risks were often just unknown and the benefits obvious.

  • IAEA Training Course: Radiation Protection in Radiotherapy

  • RADIOSENSIBILITATEAProbabilitatea ca o celul, un esut sau un organ s sufere un efect n relaie cu doza primit legea lui Bergoni i Tribondeau 1906 Cu ct o celul este mai:

    Tnr, Puin difereniat, Activ din punct de vedere mitotic;Cu att ea este mai RADIOSENSIBIL

    IAEA Training Course: Radiation Protection in Radiotherapy

  • RADIOSENSIBILITATE

    MAREMedieSczut Mduva hematogenSplinaTimusGanglioni limfaticiGonadeCristalinLimfocite (exceptie la regula radiosensibilitatii)Pieleorgane cu mezoderm (ficat, inim, plmn)MuchiOaseSistem nervos

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Tipuri de leziuni- leziuni simple - cu ruptura unui brat de AND- leziune dubla - cu degradarea a 2 filamente- leziuni incrucisate - aparitia de legaturi covalente intre proteinele de legatura, sau formarea de dimeri intre 2 baze adiacente .

    IAEA Training Course: Radiation Protection in Radiotherapy

  • RSPUNS ADAPTATIVRspunsul adaptativ presupune:Inducerea rapid a reparrii ADN fr erori, dup expuneri anterioare la doze subletale, mici de radiaii ionizante;Reducerea formrii de micronuclei, cnd expunerea acut survine dup o perioad de expuneri la doze mici;Reducerea formrii de micronuclei imediat dup o expunere cronic.

    IAEA Training Course: Radiation Protection in Radiotherapy

  • EFECTE LA NIVEL CELULARMOARTE CELULAR RADIOINDUS MODIFICRI FUNCIONALE CELULARE MUTAIICANCERIZRI

    IAEA Training Course: Radiation Protection in Radiotherapy

  • MANIFESTRI ALE EFECTELOR PE ESUT

    - HIPOPLAZIA- APLAZIA- DISPLAZIA- INSUFICENE FUNCIONALE- FIBROZ- NECROZ

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Efecte deterministiceSe datoreaz morii celulelorAu o doza pragSunt specifice pe tipul de esutSeveritatea efectului este dependenta de dozaAfectiune indusa de radiatii ionizante de la o sursa industriala

  • Exemple de efectedeterministiceModificri cutanateCataractaSterilitateInsuficienta renalaSindromul acut de iradiere (ntreg corpul)

    IAEA Training Course: Radiation Protection in RadiotherapyNote also tumor cure is in this context a deterministic effect

  • Reacii la nivel cutanat

    Afectare cutanatadupa un examenfluoroscopicprelungit

    IAEA Training Course: Radiation Protection in Radiotherapy

    Sheet1

    Radrisk.xls2/10/01

    Reference [47, Table 4-3], [48, Figure 4], [w-y] Cancer Excess Mortality (Attributable to Radiation Dose) and Years of Life Lost by Age at Exposure (death per Sv)

    Age at exposureMale Mortality, all cancers (death per Sv)Female Mortality, all cancers (death per Sv)Age range at exposureMean Age of Range at ExposureAverage years of life remaining (male) [42], [z]Average years of life remaining (female) [42], [z]Male Mortality, all cancers [x] (death per Sv)Female Mortality, all cancers [x] (death per Sv)Years of Life Lost (male) [aa]Years of Life Lost (female) [aa]

    85855.316.660.0110.0090.000.00

    Tip de afectiuneDoza prag la piele(Sv)Sapt. pana la aparitie

    eritem tranzitor precoce252

    descuamare umeda154

    eritem tardiv156-10

    necroza dermica18>10

    ulceratii secundare20>6

    [w] The mortality risk values for ages

  • EFECTELE LA NIVELUL ESUTULUI CUTANATConform legii Bergonie-Tribondeau, cele mai radiosensibile celule sunt cele din stratul bazal al epidermului

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Doza prag pentru efectele deterministice Cataracta 2-10 GySterilitate permanentaBarbati 3.5-6 Gy Femei 2.5-6 GySterilitate temporaraBarbati 0.15 GyFemei 0.6 Gy

    IAEA Training Course: Radiation Protection in RadiotherapyThis slide is useful to recap the concept of deterministic effects. Below a certain threshold there is no effect and beyond the threshold the effect becomes noticeable. There can be an increase in severity of the effect with dose, however, the notion of risk is not really applicable to deterministic effects.

    When discussing threshold values it is important to state the points given on the next slide.

  • EFECTE LA NIVELUL OCHIULUICristalinul are radiosensibilitate crescutCoagularea

    proteinelor apare la doze >2Gy

    IAEA Training Course: Radiation Protection in Radiotherapy

  • IAEA Training Course: Radiation Protection in Radiotherapy

  • GonadeleCelulele germinale ale aparatului reproductor sunt puternic radiosensibile. Media dozei-prag pentru sterilitate temporar cu durat de mai multe sptmni este de 0,15 Gy pentru brbai i de aproximativ 5 ori mai nalt pentru femei . Perioada de recuperare este dependent de doz i poate dura civa ani. Sterilitatea permanent este provocat de doza minim de respectiv 3,5 Gy pentru brbat i 2,5 Gy pentru femeie

    IAEA Training Course: Radiation Protection in Radiotherapy

  • RASPUNSUL INTREGULUI CORP: ADULTSindromul acut de iradiereSindromulcronic de iradiereTimp de supraviatuireDozaDoza letala 50 / 30Maduva osoasaGASTROINTESTINALSNC(central nervous system)1-10 Gy6-10 Gy> 50 GyManifestari clinice la nivelul intregului organism dupa o expunere partialaMecanism: Tulburari neurovegetative Similar cu o stare de rau generalApare frecvent in radioterapia cu doze fractionate

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Efectele biologice La doze mici afectarea celulelor este un efect intamplator

    chiar daca exista depozitare de energie sau nu.

    IAEA Training Course: Radiation Protection in RadiotherapyThis slide can be used with a powerpoint effect - each mouseclick will bring up one event. Alternatively, the effect can be turned off.

  • ordine de mrime1cm3 de esut = 109 celule1 mGy -->o celula din 1000 sau 106 sunt intite999 din 1000 leziuni se repara, lsnd 103 celule afectate999 din cele 1000 de celule afectate mor (nu e o problema majora pentru ca fiecare persoana pierde zilnic milioane de celule)o celula afectata poate supravieui cu modificri (poate supravieui cu mutaii)

    IAEA Training Course: Radiation Protection in RadiotherapyThese are obviously only rough estimates - however they may illustrate the magnitude of the problem. It could be pointed out that 1mGy is of the order of magnitude of the annual exposure of humans. Therefore the whole discussion above could be made for 1 year of life.

  • Inducerea canceruluiEste cel mai important efect stocastic din punct de vedere al proteciei radiologiceEste un proces multistadial tipic in trei etape: fiecare etapa necesita un evenimentEste un proces complicat care implica celulele, comunicarea intre celule si sistemul imun...

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Cuantificarea efectelor stocasticeRiscul de deces prin cancer pe durata ntregii viei la populaia generala este de = 5% / SvRiscul de cancer fatal pe durata ntregii viei pentru cancer de:Mduva osoasa0.5 % / SvSuprafaa osului0.05San 0.2 %plmn0.85tiroida0.08

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Sursele de expunere naturala

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Contribuia expunerii la radiaii in UKTotal: 2-3mSv/an

    IAEA Training Course: Radiation Protection in RadiotherapyThis is only an example - other countries and even areas in different countries can have quite different radiation exposures due to natural sources.

  • DOZELE MICI Definitii:- dozele totale sub 10 mSv primite la o rata a dozei inalta in timpul unui eveniment- doze mai mici de 20 mSv primite intr-un an, primite continuu

    IAEA Training Course: Radiation Protection in Radiotherapy

  • Ce se ntmpla in partea de jos a graficului la doze mici sub 100 mSv?

    IAEA Training Course: Radiation Protection in RadiotherapyThis slide and the one two before it are similar in contents. The lecturer can omit one.

  • Estimri de riscRisc = probabilitatea de apariie a unui efectPentru efecte diferite este important sa avem clar despre ce efect este vorba: Ex. Termenul mortalitate prin cancer tiroidian NU este identic cu incidena de cancer tiroidianEstimarea riscului se obine de obicei pornind de la doze mari si extrapolnd la dozele mici

    IAEA Training Course: Radiation Protection in Radiotherapy

  • EFECTELE EXPUNERII ANTENATALEEFECTE LETALEPot sa apar la doze relativ mici (0,1 Gy) n timpul preimplantrii sau implantrii embrionului n peretele uterinPot sa apar i la doze mari n timpul celorlalte stadii de dezvoltare intra-uterin

    IAEA Training Course: Radiation Protection in Radiotherapy

  • ConcluziiInducerea cancerului este riscul cel mai important in expunerea la radiaii ionizante la doze miciInducerea cancerului este un efect stocasticLa doze mari apar efecte deterministice

    IAEA Training Course: Radiation Protection in RadiotherapyLets summarize the main subjects we did cover in this lecture

  • Concluzii Riscurile pot fi calculateDe altfel:cifrele sunt de obicei mici si s-ar putea sa nu aib vreo semnificaie deosebita pentru oricineAciunile ntreprinse pentru a evita sau a reduce la minim riscurile depind de interpretare si de beneficiile percepute - acestea pot varia semnificativ de la o persoana la alta sau intre societatiCostrangerile de doza pot fi alese pentru a le compara cu riscurile din alte profesii

    IAEA Training Course: Radiation Protection in Radiotherapy

  • ntrebri?

    IAEA Training Course: Radiation Protection in Radiotherapy

    Part No 3, Lesson No 1Deterministic effects are for example:skin reddening (erythema)skin breakdown (desquamation)cataracts in the lens of the eyetumor cell killdeath

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1The major stochastic effect is cancer induction - however, also many hereditary effects are stochastic. The risk of having a malformation in a baby increases with dose- the severity of the event though is independent of it.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1The lecturer can again point out the stochastic nature of the energy deposition on the scale of dimensions of a cell. In particular at low doses there may or may not be an interaction in a given nucleus. The last slide of the dosimetry lecture is repeated as next slide - hidden. The lecturer can unhide it if deemed appropriate.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1The discussion on how much each of the two effects - indirect and direct damage to DNA contribute to cell kill is still ongoing. In practice both play a role.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1The lecturer should point out that this was not necessarily bad practice - radiation risks were often just unknown and the benefits obvious.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1Note also tumor cure is in this context a deterministic effectIAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1This slide is useful to recap the concept of deterministic effects. Below a certain threshold there is no effect and beyond the threshold the effect becomes noticeable. There can be an increase in severity of the effect with dose, however, the notion of risk is not really applicable to deterministic effects.

    When discussing threshold values it is important to state the points given on the next slide.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1This slide can be used with a powerpoint effect - each mouseclick will bring up one event. Alternatively, the effect can be turned off.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1These are obviously only rough estimates - however they may illustrate the magnitude of the problem. It could be pointed out that 1mGy is of the order of magnitude of the annual exposure of humans. Therefore the whole discussion above could be made for 1 year of life.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1This is only an example - other countries and even areas in different countries can have quite different radiation exposures due to natural sources.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1This slide and the one two before it are similar in contents. The lecturer can omit one.IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1Lets summarize the main subjects we did cover in this lectureIAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in RadiotherapyPart No 3, Lesson No 1

    IAEA Training Material: Radiation Protection in Radiotherapy