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Efectos biológicos de las radiaciones
ionizantes
1
Presentado por Blgo. Marco E. Espinoza
31 de Mayo 2008 – CSEN - IPEN
Wilhelm Roentgen
Discovered X-rays on 8th
November 1895
2
Henri Becquerel
Discovered radioactivity on
26 February 1896
3
Frau Roentgen’s hand, 1895 Colles’ fracture 1896
5
X - actly So!
The Roentgen Rays, the Roentgen Rays,
What is this craze?
The town's ablaze
With the new phase
Of X-ray's ways.
I'm full of daze,
Shock and amaze;
For nowadays
I hear they'll gaze
Thro' cloak and gown and even stays,
Those naughty, naughty Roentgen Rays.
(Wilhelma, Electrical Review, April 1896)
First Reports of Injury
Late 1896
Elihu Thomson - burn from deliberate
exposure of finger
6
Edison’s assistant - hair fell out & scalp
became inflamed & ulcerated
7
Mihran Kassabian (1870-1910)
8
Sister Blandina
(1871 - 1916)
• 1898, started work as radiographer in
Cologne
• held nervous patients & children with
unprotected hands
• controlled the degree of hardness of
the X-ray tube by placing her hand
behind of the screen.
09/06/2008 9
Sister Blandina
• After 6 months strong flushing & swellings of hands
• diagnosed with an X-ray cancer,
• some fingers amputated
• then whole hand amputated
• whole arm amputated.
09/06/2008 10
Sister Blandina
• 1915 severed difficulties of breathing
• extensive shadow on the left side of her thorax
• large wound on her whole front- and back-side
• Died on 22nd October 1916 .
09/06/2008 11
William Rollins
Rollins W. X-light kills. Boston Med Surg J
1901;144:173.
Codman EA. No practical danger from the
x-ray. Boston Med Surg J 1901;144:197
09/06/2008
12
Mechanisms of Radiation Injury
13
„ LD(50/30) = 4 Gy
≅ 280 J to 70 kg man
≅ 1 milli-Celsius rise in body temp.
≅ drinking 6 ml of warm tea
i.e. not caused by heating, but ionisation.
09/06/2008
14
15
Methods of Potential Damage from
Ionizing Radiation
• Indirect Action
assumes cellular damage occurs as a
result of the action of radiation on water
(roughly 85% of a cell’s composition);
damage results from the indirect action
of toxic compounds on cellular DNA
Radicales Libres
16
„ H2O + γ → H2O+ + e-
• H2O+ → OH• + H+
„ OH• + e- → OH- (radical hidroxilo)
„ H+ + H2O → H3O+
„ OH• + OH• → H2O2 (peróxido de hidrógeno)
„ O2 + e- → O2
- (produce radicales peroxilo)
Los efectos sobre las células
17
„ Muerte celular después de mitosis anormales.
„ Muerte celular antes de la mitosis.
„ Mitosis anormales a pesar de acciones de reparación
celular.
„ Mitosis anormales, sin muerte celular, con replicación del
daño en las generaciones futuras.
„ Síntesis tardía de ADN o mitosis muy lentas.
„ Cambios en el protoplasma celular durante la mitosis que
alteran el proceso de la citocinesis.
Ley de Bergonié y Tribondeau (1906)
18
„ En términos generales las células tienden a ser
radiosensibles si tienen tres propiedades:
1. Una alta tasa de división mitótica
2. Una vida futura larga en permanente división
3. Son células no especializadas.
Hay tres importantes excepciones: Linfocitos pequeños, oocitos primarios y
neuroblastos.
19
Radiosensibilidad relativa de las
células comunes
Baja: Células sanguíneas maduras, células
musculares, células ganglionares, tejidos
conectivos maduros
Alta: mucosa gástrica, membranas mucosas,
epitelio esofágico, epitelio de la vejiga urinaria
Muy alta: células sanguíneas primordiales, epitelio
intestinal, espermatogonias, células foliculares
ováricas, linfocitos.
Dos tipos de efecto
•Efectos determinísticos (“efectos con umbral”)
• Llamados también “tempranos” o “ agudos”
•Efectos estocásticos (“efectos al probabilísticos”)
• Conocidos también como efectos “tardíos” o “a largo plazo”
09/06/2008
20
Deterministic Effects
09/06/2008
21
„Caused by significant cell necrosis
„Not seen below a threshold dose
„Above the threshold, the bigger the
dose, the worse the effect
09/06/2008
22
Categories of Radiation Bioeffects :
Deterministic (Nonstochastic) Effects
Those effects whose severity increases with
increases in dose; a threshold dose is
assumed (e.g., erythema, cataract
formation, blood effects)
Stochastic Effects
09/06/2008
23
„Caused by cell mutation leading to cancer
or hereditary disease
„Current theory says, no threshold
„The bigger the dose, the more likely
effect.
09/06/2008
24
Categories of Radiation Bioeffects :
Stochastic Effects
Those effects that appear to be random in
nature; effects that tend to increase with
increasing dose to the population (e.g.,
cancer and genetic effects)
ICRP risk factors
(International Commission on Radiological
Protection, ICRP Publication 60)
25
Detriment per mSv
Exposed Population Fatal cancer Non-fatal cancer Severed hereditary
effects
Total
Adult workers 4.0 x 10-5
0.8 x 10-5
0.8 x 10-5
5.6 x 10-5
Whole population 5.0 x 10-5
1.0 x 10-5
1.3 x 10-5
7.3 x 10-5
(fetus 3.0 x 10-5
3.0 x 10-5
6.0 x 10-5
)
5.0 x 10-5 per mSv ≡ 1 in 20,000 chance .
09/06/2008
26
Explosiones Atómicas: 6 Aug 1945 Hiroshima - 9 Aug 1945 Nagasaki
70 000 murieron inmediatamente y 200 000 en los 4 meses siguientes
100 000 personas que recibieron más de 200 mSv, sobrevivieron. Las víctimas de
las bombas fueron estudiados y tienen un seguimiento de por vida.
09/06/2008
27
Evidencias de los efectos estocásticos:
Estudio de la expectativa de vida de un grupo
de sobrevivientes de las bombas atómicas
09/06/2008
28
„ Se estudió a 94 000 personas
„ Más del 50% todavía vivían en 1995
„ Para 1991 cerca de 8 000 habían muerto por cáncer
„ Unos 430 de esos cánceres podían ser atribuibles a la
radiación.
„ 21 de 800 personas expuestas in utero con dosis mayores a
10 mSv resultaron severamente afectados con retardo
mental.
„ No se demostró incremento de las frecuencias
poblacionales de las enfermedades de origen genético.
„ http://www.rerf.or.jp/eigo/glossary/lsspopul.htm
Dose range Number of
cancer deaths
Estimated
excess death
Attributable
fraction
5 - 200 mSv 3391 63 2 %
00 - 500 mSv 646 76 12 %
0.5 - 1 Sv 342 79 23 %
> 1 Sv 308 121 39 %
All 4687 339 7 %
09/06/2008
29
Cancer deaths between 1950 and 1990 among Life Span Study
survivors with significant exposure
(i.e. > 5 mSv or within 2.5 km of the hypercentre)
Data Sources for Risk Estimates
09/06/2008
30
„North American patients - breast, thyroid, skin
„German patients with Ra-224 - bone
„Euro. Patients with Thorotrast - liver
„Oxford study - in utero induced cancer
„Atomic bomb survivors - leukaemia, lung, colon,
stomach, remainder .
09/06/2008
31
Linear Dose Response Curve:
Probability of
Observing the
Response
Dose
Assumes some level of hazard is associated with
all doses regardless of how small.
09/06/2008
32
Linear Dose Response Implications and
Assumptions:
• Certain effects (e.g., leukemia, genetic effects) are
observed even at zero radiation dose since it occurs
naturally in populations (stochastic effects)
• Assumes the probability of observing the response
is proportional to the dose
• This theory is the basis of radiation protection
programs
09/06/2008
33
Nonlinear Threshold Dose Response:
Threshold
Response
Dose
Assumes there exists some minimal (threshold) dose
below which no observable effects occur.
09/06/2008
34
Nonlinear Threshold Dose Response Implications
and Assumptions:
• This type of response curve more accurately
describes bioeffects associated with high doses (e.g.,
blood changes, GI effects, epilation, organ damage,
etc.) - Deterministic or certainty effects
• Assumes recovery from bioeffects at low doses
(i.e., in the dose range below the threshold)
Doses in Interventional Radiology
Taken from “Real-time quantification and display of skin radiation during coronary angiography and intervention”,
den Boer A, et al., Oct 2001
35
09/06/2008
•332 patients
•25 - 99 Gy.cm2 dose-area product
•4 - 18 mGy effective dose
•1:5000 - 1:1100 risk of inducing fatal cancer
.
Hereditary Effects
09/06/2008
36
„ Observed in animal experiments
„ Not observed in A-bomb victims
„ ICRP Detriment for severe hereditary disease = 1.3 x 10-5 per
mSv (i.e. approx 1/4 fatal cancer risk)
09/06/2008
37
Total risk of cancer up to age 15 years following in utero exposure (per mGy)
Cancer type Fatal Non-fatal Total
Leukaemia 1.25 × 10
-5
1.25 × 10
-5
2.5 × 10
-5
Other 1.75 × 10
-5
1.75 × 10
-5
3.5 × 10
-5
Total 3.0 × 10
-5
3.0 × 10
-5
6.0 × 10
-5
• at 8-15 weeks it is estimated that 30 IQ points are lost per 1000 mGy.
• Risk of heritable effects estimated at 2.4 × 10
-5
per mGy
"Natural Risks"
Heritable disease 1 × 10
-2
to 6 × 10
-2
Fatal cancer to age 15 years 7.7 × 10
-4
Lifetime cancer risk 20 × 10
-2
to 25 × 10
-2
FETAL DOSES FROM MEDICAL EXPOSURE (mGy)
Examination Mean Max.
Conventional X-ray
Abdomen (AP only) 1.4 4.2
Barium enema 6.8 24
Barium meal 1.1 5.8
Chest < 0.01 < 0.01
Intravenous urography 1.7 10
Lumbar spine 1.7 10
Pelvis 1.1 4
Skull < 0.01 < 0.01
Thoracic spine < 0.01 < 0.01
CT
Abdomen 8 49
Chest 0.06 0.96
Head < 0.005 < 0.005
Pelvis 25 79
Pelvimetry 0.2 0.4
09/06/2008
38
FETAL DOSES FROM MEDICAL EXPOSURE (mGy)
Examination Mean Max.
Nuclear Medicine
99m
Tc bone scan (phosphate) 3.3 4.6
99m
Tc lung perfusion (MAA) 0.2 0.4
99m
Tc lung ventilation (aerosol) 0.3 1.2
99m
Tc kidney scan (DTPA) 1.5 4
99m
Tc thyroid scan (pertechnetate) 0.7 1.6
99m
Tc dynamic cardiac scan (RBC) 3.4 3.7
51
Cr glomerular filtration (EDTA) < 0.01 0.01
201
Tl myocardial perfusion (thallium) 3.7 4
99m
Tc brain scan (pertechnetate) 4.3 6.5
75
Seleno-cholesterol - 14
67
Ga tumours and abscesses - 12
131
I thyroid metastases - 22
09/06/2008
39
EXAMPLES OF RISK OF CHILDHOOD CANCER
•“Natural” risk: 1 in 1,300
•Abdomen mean: 1.4 mGy → 1 in 24,000
max.: 4.2 mGy → 1 in 8,000
•CT Abdomen mean: 8 mGy → 1 in 4,000
max.: 49 mGy → 1 in 700
•Pelvis mean: 1.1 mGy → 1 in 30,000
max.: 4.0 mGy → 1 in 8,000
•CT Pelvis mean: 8 mGy → 1 in 4,000
max.: 79 mGy → 1 in 400
09/06/2008
40

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001 Efectos Biológicos de las radiaciones ionizantes.pdf

  • 1. Efectos biológicos de las radiaciones ionizantes 1 Presentado por Blgo. Marco E. Espinoza 31 de Mayo 2008 – CSEN - IPEN
  • 2. Wilhelm Roentgen Discovered X-rays on 8th November 1895 2
  • 4. Frau Roentgen’s hand, 1895 Colles’ fracture 1896
  • 5. 5 X - actly So! The Roentgen Rays, the Roentgen Rays, What is this craze? The town's ablaze With the new phase Of X-ray's ways. I'm full of daze, Shock and amaze; For nowadays I hear they'll gaze Thro' cloak and gown and even stays, Those naughty, naughty Roentgen Rays. (Wilhelma, Electrical Review, April 1896)
  • 6. First Reports of Injury Late 1896 Elihu Thomson - burn from deliberate exposure of finger 6 Edison’s assistant - hair fell out & scalp became inflamed & ulcerated
  • 7. 7
  • 9. Sister Blandina (1871 - 1916) • 1898, started work as radiographer in Cologne • held nervous patients & children with unprotected hands • controlled the degree of hardness of the X-ray tube by placing her hand behind of the screen. 09/06/2008 9
  • 10. Sister Blandina • After 6 months strong flushing & swellings of hands • diagnosed with an X-ray cancer, • some fingers amputated • then whole hand amputated • whole arm amputated. 09/06/2008 10
  • 11. Sister Blandina • 1915 severed difficulties of breathing • extensive shadow on the left side of her thorax • large wound on her whole front- and back-side • Died on 22nd October 1916 . 09/06/2008 11
  • 12. William Rollins Rollins W. X-light kills. Boston Med Surg J 1901;144:173. Codman EA. No practical danger from the x-ray. Boston Med Surg J 1901;144:197 09/06/2008 12
  • 13. Mechanisms of Radiation Injury 13 „ LD(50/30) = 4 Gy ≅ 280 J to 70 kg man ≅ 1 milli-Celsius rise in body temp. ≅ drinking 6 ml of warm tea i.e. not caused by heating, but ionisation.
  • 15. 15 Methods of Potential Damage from Ionizing Radiation • Indirect Action assumes cellular damage occurs as a result of the action of radiation on water (roughly 85% of a cell’s composition); damage results from the indirect action of toxic compounds on cellular DNA
  • 16. Radicales Libres 16 „ H2O + γ → H2O+ + e- • H2O+ → OH• + H+ „ OH• + e- → OH- (radical hidroxilo) „ H+ + H2O → H3O+ „ OH• + OH• → H2O2 (peróxido de hidrógeno) „ O2 + e- → O2 - (produce radicales peroxilo)
  • 17. Los efectos sobre las células 17 „ Muerte celular después de mitosis anormales. „ Muerte celular antes de la mitosis. „ Mitosis anormales a pesar de acciones de reparación celular. „ Mitosis anormales, sin muerte celular, con replicación del daño en las generaciones futuras. „ Síntesis tardía de ADN o mitosis muy lentas. „ Cambios en el protoplasma celular durante la mitosis que alteran el proceso de la citocinesis.
  • 18. Ley de Bergonié y Tribondeau (1906) 18 „ En términos generales las células tienden a ser radiosensibles si tienen tres propiedades: 1. Una alta tasa de división mitótica 2. Una vida futura larga en permanente división 3. Son células no especializadas. Hay tres importantes excepciones: Linfocitos pequeños, oocitos primarios y neuroblastos.
  • 19. 19 Radiosensibilidad relativa de las células comunes Baja: Células sanguíneas maduras, células musculares, células ganglionares, tejidos conectivos maduros Alta: mucosa gástrica, membranas mucosas, epitelio esofágico, epitelio de la vejiga urinaria Muy alta: células sanguíneas primordiales, epitelio intestinal, espermatogonias, células foliculares ováricas, linfocitos.
  • 20. Dos tipos de efecto •Efectos determinísticos (“efectos con umbral”) • Llamados también “tempranos” o “ agudos” •Efectos estocásticos (“efectos al probabilísticos”) • Conocidos también como efectos “tardíos” o “a largo plazo” 09/06/2008 20
  • 21. Deterministic Effects 09/06/2008 21 „Caused by significant cell necrosis „Not seen below a threshold dose „Above the threshold, the bigger the dose, the worse the effect
  • 22. 09/06/2008 22 Categories of Radiation Bioeffects : Deterministic (Nonstochastic) Effects Those effects whose severity increases with increases in dose; a threshold dose is assumed (e.g., erythema, cataract formation, blood effects)
  • 23. Stochastic Effects 09/06/2008 23 „Caused by cell mutation leading to cancer or hereditary disease „Current theory says, no threshold „The bigger the dose, the more likely effect.
  • 24. 09/06/2008 24 Categories of Radiation Bioeffects : Stochastic Effects Those effects that appear to be random in nature; effects that tend to increase with increasing dose to the population (e.g., cancer and genetic effects)
  • 25. ICRP risk factors (International Commission on Radiological Protection, ICRP Publication 60) 25 Detriment per mSv Exposed Population Fatal cancer Non-fatal cancer Severed hereditary effects Total Adult workers 4.0 x 10-5 0.8 x 10-5 0.8 x 10-5 5.6 x 10-5 Whole population 5.0 x 10-5 1.0 x 10-5 1.3 x 10-5 7.3 x 10-5 (fetus 3.0 x 10-5 3.0 x 10-5 6.0 x 10-5 ) 5.0 x 10-5 per mSv ≡ 1 in 20,000 chance .
  • 26. 09/06/2008 26 Explosiones Atómicas: 6 Aug 1945 Hiroshima - 9 Aug 1945 Nagasaki 70 000 murieron inmediatamente y 200 000 en los 4 meses siguientes 100 000 personas que recibieron más de 200 mSv, sobrevivieron. Las víctimas de las bombas fueron estudiados y tienen un seguimiento de por vida.
  • 28. Evidencias de los efectos estocásticos: Estudio de la expectativa de vida de un grupo de sobrevivientes de las bombas atómicas 09/06/2008 28 „ Se estudió a 94 000 personas „ Más del 50% todavía vivían en 1995 „ Para 1991 cerca de 8 000 habían muerto por cáncer „ Unos 430 de esos cánceres podían ser atribuibles a la radiación. „ 21 de 800 personas expuestas in utero con dosis mayores a 10 mSv resultaron severamente afectados con retardo mental. „ No se demostró incremento de las frecuencias poblacionales de las enfermedades de origen genético. „ http://www.rerf.or.jp/eigo/glossary/lsspopul.htm
  • 29. Dose range Number of cancer deaths Estimated excess death Attributable fraction 5 - 200 mSv 3391 63 2 % 00 - 500 mSv 646 76 12 % 0.5 - 1 Sv 342 79 23 % > 1 Sv 308 121 39 % All 4687 339 7 % 09/06/2008 29 Cancer deaths between 1950 and 1990 among Life Span Study survivors with significant exposure (i.e. > 5 mSv or within 2.5 km of the hypercentre)
  • 30. Data Sources for Risk Estimates 09/06/2008 30 „North American patients - breast, thyroid, skin „German patients with Ra-224 - bone „Euro. Patients with Thorotrast - liver „Oxford study - in utero induced cancer „Atomic bomb survivors - leukaemia, lung, colon, stomach, remainder .
  • 31. 09/06/2008 31 Linear Dose Response Curve: Probability of Observing the Response Dose Assumes some level of hazard is associated with all doses regardless of how small.
  • 32. 09/06/2008 32 Linear Dose Response Implications and Assumptions: • Certain effects (e.g., leukemia, genetic effects) are observed even at zero radiation dose since it occurs naturally in populations (stochastic effects) • Assumes the probability of observing the response is proportional to the dose • This theory is the basis of radiation protection programs
  • 33. 09/06/2008 33 Nonlinear Threshold Dose Response: Threshold Response Dose Assumes there exists some minimal (threshold) dose below which no observable effects occur.
  • 34. 09/06/2008 34 Nonlinear Threshold Dose Response Implications and Assumptions: • This type of response curve more accurately describes bioeffects associated with high doses (e.g., blood changes, GI effects, epilation, organ damage, etc.) - Deterministic or certainty effects • Assumes recovery from bioeffects at low doses (i.e., in the dose range below the threshold)
  • 35. Doses in Interventional Radiology Taken from “Real-time quantification and display of skin radiation during coronary angiography and intervention”, den Boer A, et al., Oct 2001 35 09/06/2008 •332 patients •25 - 99 Gy.cm2 dose-area product •4 - 18 mGy effective dose •1:5000 - 1:1100 risk of inducing fatal cancer .
  • 36. Hereditary Effects 09/06/2008 36 „ Observed in animal experiments „ Not observed in A-bomb victims „ ICRP Detriment for severe hereditary disease = 1.3 x 10-5 per mSv (i.e. approx 1/4 fatal cancer risk)
  • 37. 09/06/2008 37 Total risk of cancer up to age 15 years following in utero exposure (per mGy) Cancer type Fatal Non-fatal Total Leukaemia 1.25 × 10 -5 1.25 × 10 -5 2.5 × 10 -5 Other 1.75 × 10 -5 1.75 × 10 -5 3.5 × 10 -5 Total 3.0 × 10 -5 3.0 × 10 -5 6.0 × 10 -5 • at 8-15 weeks it is estimated that 30 IQ points are lost per 1000 mGy. • Risk of heritable effects estimated at 2.4 × 10 -5 per mGy "Natural Risks" Heritable disease 1 × 10 -2 to 6 × 10 -2 Fatal cancer to age 15 years 7.7 × 10 -4 Lifetime cancer risk 20 × 10 -2 to 25 × 10 -2
  • 38. FETAL DOSES FROM MEDICAL EXPOSURE (mGy) Examination Mean Max. Conventional X-ray Abdomen (AP only) 1.4 4.2 Barium enema 6.8 24 Barium meal 1.1 5.8 Chest < 0.01 < 0.01 Intravenous urography 1.7 10 Lumbar spine 1.7 10 Pelvis 1.1 4 Skull < 0.01 < 0.01 Thoracic spine < 0.01 < 0.01 CT Abdomen 8 49 Chest 0.06 0.96 Head < 0.005 < 0.005 Pelvis 25 79 Pelvimetry 0.2 0.4 09/06/2008 38
  • 39. FETAL DOSES FROM MEDICAL EXPOSURE (mGy) Examination Mean Max. Nuclear Medicine 99m Tc bone scan (phosphate) 3.3 4.6 99m Tc lung perfusion (MAA) 0.2 0.4 99m Tc lung ventilation (aerosol) 0.3 1.2 99m Tc kidney scan (DTPA) 1.5 4 99m Tc thyroid scan (pertechnetate) 0.7 1.6 99m Tc dynamic cardiac scan (RBC) 3.4 3.7 51 Cr glomerular filtration (EDTA) < 0.01 0.01 201 Tl myocardial perfusion (thallium) 3.7 4 99m Tc brain scan (pertechnetate) 4.3 6.5 75 Seleno-cholesterol - 14 67 Ga tumours and abscesses - 12 131 I thyroid metastases - 22 09/06/2008 39
  • 40. EXAMPLES OF RISK OF CHILDHOOD CANCER •“Natural” risk: 1 in 1,300 •Abdomen mean: 1.4 mGy → 1 in 24,000 max.: 4.2 mGy → 1 in 8,000 •CT Abdomen mean: 8 mGy → 1 in 4,000 max.: 49 mGy → 1 in 700 •Pelvis mean: 1.1 mGy → 1 in 30,000 max.: 4.0 mGy → 1 in 8,000 •CT Pelvis mean: 8 mGy → 1 in 4,000 max.: 79 mGy → 1 in 400 09/06/2008 40