Learning Objectives
Review of the
Radiobiological Principles of
Radiation Protection
1. To understand the radiobiological basis
of radiation protection standards.
2. To define the radiation protection
magnitudes and units, their values and
their practical measurement.
Cari Borrás, D.Sc., FAAPM, FACR
Radiological Physics and Health Services Consultant
Washington DC, USA
3. To distinguish between stochastic and
deterministic effects.
1
Interaction of ionizing radiation with
DNA, the critical target
Radiation Effects
Ionizing radiation
interacts at the
cellular level:
•
•
•
ionization
chemical changes
biological effect
cell
nucleus
incident
radiation
chromosomes
http://rpop.iaea.org/
2
DIRECT ACTION
3
http://rpop.iaea.org/
INDIRECT ACTION
4
Indirect action of radiation
Direct action of radiation
Consider water
H2O  H2O+ + e
•
Predominant for high LET radiation, particulates
Water molecule becomes ionized to a free radical (unpaired electron)
and an ion (loss of an electron). These are highly reactive, short
lifetime
•
High LET radiations interact predominately with
nuclei
H2O+ + H2O  H3O+ + OH
•
•
•
•
•
•
diffusion distance twice diameter of DNA helix
estimated 2/3 of x-ray damage in mammalian cells from
hydroxyl radicals
less indirect action for high LET radiation
chemical sensitizers exploit indirect damage
protectors act against radicals
http://rpop.iaea.org/
•
•
5
6
DNA Damage
There are qualitative and quantitative
differences in initial DNA damage caused by
radiation
Unviable Cell
Cell dies
Cell mutates
but mutation
is repaired
Not modified by sensitizers or protectors
http://rpop.iaea.org/
Outcomes after Cell Exposure
Radiation
hits cell
nucleus!
setting in motion more protons and other heavier nuclear
particles
smaller particles (electrons) are produced which cause
indirect damage but this is less significant c.f. direct action
Viable Cell
Cancer?

DNA damage caused by radiation exhibits multiply damaged
sites and clustered legions

Double strand breaks are more common in radiation-induced
damage than single strand breaks, which are more common
in normal endogenous DNA damage.
Cell survives
but mutated
http://rpop.iaea.org/
7
http://lowdose.energy.gov/pdf/Powerpoint_WEBBystander.pdf
8
10-15
How does radiation interact
with cells?
Energy deposition
Excitation/ionization
10-12
Initial particle tracks
10-9
Radical formation
Diffusion, chemical reactions
Present Theories
Hit theory
Bystander effects
Radiation causes free
radicals to damage only
the cell that is “hit” by
direct ionization
Radiation causes free
radicals to trigger cell-cell
communication and cellmatrix communication to
cells other than those
which are “hit” by the
direct ionization.
http://lowdose.energy.gov/pdf/Powerpoint_WEBBystander.pdf
ICRP reviewed new radiobiology data since 1991
▲
Changed
▲
▲
•
•
•
100
1 second
DNA breaks / base damage
Repair processes
Damage fixation
1 hour
Cell killing
1 day
Mutations/transformations/aberrations
Proliferation of "damaged" cells
Promotion/completion
1 year
BIOLOGICAL RESPONSE
Teratogenesis
MEDICAL EFFECTS
Cancer
Hereditary defects
109
100 years
Timing of
events
leading to
radiation
effects.
9
10
RP Dosimetric Quantities and Units
▲
Incorporate Exposures
•
•
Radiation-weighting factors (wR)
Tissue-weighting factors (wT)
Risk of cancer induction rather than mortality
▲
Radiation protection principles, (i.e. LNT)
Dose limits
Radiation quantities and units, accepting ICRU
operational quantities for compliance with dose limits
External
Internal
Are Different For:
•
Did not change
•
•
•
1 ms
106
The 2007 (ICRP 103) Recommendations
▲
10-3
103
PHYSICO-CHEMICAL INTERACTIONS
Initial DNA damage
10-6
TIME (sec)
Past Theory
PHYSICAL INTERACTIONS
Low doses of (low-LET) radiation < 0.5 Gy
o
•
Emphasized dose constraints
•
Cancer induction
•
Hereditary diseases
High doses of radiation
o
11
Stochastic (probabilistic) effects, LNT is applicable
Tissue reactions (deterministic effects), threshold exists
12
RP Dosimetric Quantities and Units
RP Dosimetric Quantities and Units
Tissue Reactions
Stochastic Effects
Evolution of Terminology
Dose to Tissue = Absorbed Dose * RBE (Gy)
ICRP 26 (1977)
ICRP 60 (1991)
ICRP 103 (2007)
RBE : radiobiological effectiveness
*
Equivalent Dose
Equivalent Dose#
differs for
Effective Dose
Equivalent
Effective Dose
Effective Dose
•
•
different biological endpoints and
different tissues or organs
#
* No specific term
Radiation Weighted Dose proposed but not accepted
The SI unit is J kg-1 and the special name is sievert (Sv)
13
RP Dosimetric Quantities and Units
Stochastic Effects (Sv)
Radiation Weighting Factors (ICRP 103)
Radiation type and energy range
Equivalent Dose, HT, in a tissue T:
Photons
HT = ΣR wR D T,R
Electrons and muons
Protons (1991, 2007), pions (2007)
Alpha particles, fission fragments, heavy ions
Neutrons, energy
< 10 keV
10 keV to 100 keV
D T,R is the absorbed dose averaged over the tissue
T due to radiation R
> 100 keV to 2 MeV
> 2 MeV to 20 MeV
wR
1
1
2
20
Continuous
Function
wR is the radiation weighting factor, which accounts for
the detriment caused by different types of radiation
relative to photon irradiation
wR values are derived from in vivo and in vitro RBE studies
They are independent of dose and dose rate in the low dose region
14
> 20 MeV
15
16
RP Dosimetric Quantities and Units
Stochastic Effects (Sv)
Effective Dose, E
E = ΣT wT H T = ΣT ΣR wT wR D R,T
wT represents the relative contribution of that
tissue or organ to the total detriment resulting
from uniform irradiation of the body
ΣT wT = 1
17
Tissue Weighting Factors
(ICRP 103)
A uniform dose distribution in the whole body gives
an effective dose numerically equal to the radiationweighted dose in each organ and tissue of the body
RP Dosimetric Quantities and Units
Tissue
wT
∑ wT
Bone-marrow (red), Colon, Lung, Stomach, Breast,
Remainder Tissues*
0.12
0.72
Gonads
0.08
0.08
Bladder, Oesophagus, Liver, Thyroid
0.04
0.16
Bone surface, Brain, Salivary glands, Skin
0.01
0.04
So far we have discussed external exposures
Total
1.00
Let´s see about exposures from radionuclides
*
18
▲
Incorporate Exposures
•
•
External
Internal
Remainder Tissues: Adrenals, Extrathoracic region, Gall bladder, Heart,
Kidneys, Lymphatic nodes, Muscle, Oral mucosa, Pancreas, Prostate, Small
intestine, Spleen, Thymus and Uterus/cervix
19
20
RP Dosimetric Quantities and Units
Stochastic Effects (Sv)
RP Dosimetric Quantities and Units
Activity, A
Committed Equivalent Dose
The activity A of an amount of a radionuclide
in particular energy state at a given time t is
For radionuclides
incorporated in the body
A= d N / d t
where τ is the integration time following the intake at time t0
where d N is the expectation value of the
number of spontaneous nuclear transitions
from that energy state in the time interval d t
Committed Effective Dose
τ
The SI unit of activity is the Becquerel (Bq)
Adults: 50 y
Children: 70 y
1 Bq = 1 s-1
21
Limitations of
Equivalent and Effective Doses
▲
▲
▲
22
RP Operational Quantities - ICRU
Dose Equivalent, H
Are not directly measurable
Point quantities needed for area monitoring (in
a non-isotropic radiation field, effective dose
depends on the body’s orientation in that field)
Instruments for radiation monitoring need to
be calibrated in terms of a measurable
quantity for which calibration standards exist
H = Q * D (Sv)
Where: D = Absorbed Dose
Q = Quality Factor, function of L∞ (LET)
At a point in tissue:
Operational protection quantities are needed!
23
Where: DL is the distribution
of D in L for the charged
particles contributing to D
24
Assessment of Effective Dose from
Individual Monitoring Data
•
•
H*(10) and HP (10) – photons > 12 keV and neutrons
HP (0.07) – α and β particles and doses to extremities
•
•
Ω in RP usually not specified. Instead,
•
Maximum H’(0.07, Ω) is obtained
by rotating meter seeking maximum reading
Hp (10) personal dose equivalent from external exposure
ej,inh(τ) is the committed effective dose coefficient for
activity intakes by inhalation of radionuclide j
Ij,inh is the activity intake of radionuclide j by inhalation
ej,ing(τ) is the committed effective dose coefficient for
activity intakes of radionuclide j by ingestion
Ij,ing is the activity intake of radionuclide j by ingestion
25
26
RP Dosimetric Quantities and Units
System of Quantities for Radiological Protection
Stochastic Effects
Collective Effective Dose, S
Absorbed dose, D
(due to Individual Effective Doses E1 and E2)
Dose Quantities
defined in the body
Operational
Quantities
Equivalent dose, HT, in an
organ or tissue T
For external exposure
Dose quantities for
Effective dose, E
• d N / d E : number of individuals who experience
an effective dose between E and E + d E
• ΔT specifies the time period within which the
effective doses are summed
Committed doses,
HT (τ) and E(τ)
Collective effective dose, S
27
area monitoring
individual monitoring
For internal exposure
Activity quantities in
combination with
biokinetic models and
computations
28
RP Dosimetric Quantities and Units
E is calculated averaging
gender, age and individual sensitivity
Caveats
Effective Dose should not be used for
▲
▲
▲
ICRP
Retrospective dose assessments
Estimation of specific individual human
exposures and risks
Epidemiological studies without careful
consideration of the uncertainties and
limitations of the models and values used
29
30
Effective Dose vs Organ Doses
in Medical Exposures
RP Dosimetric Quantities and Units
Caveats
Dose to Individuals
Effective Dose is an adequate parameter
Absorbed doses to organs or tissues should be
used with the most appropriate biokinetic
parameters, biological effectiveness of the
ionizing radiation and risk factor data, taking
into consideration the associated uncertainties.
to intercompare doses from different
radiological techniques
However, to assess individual risks it is
Medical exposures fall in this category!
necessary to determine organ doses
31
32
Methods for Determining Organ and
Tissue Doses (ICRU 74, 2005)
▲
▲
Measurements in physical phantoms
Monte Carlo radiation transport
calculations
•
•
•
•
Mathematical phantoms
Special features of the active bone marrow
Voxel phantoms
Anthropometric phantoms
33
34
THE AIM OF RADIATION
PROTECTION
BEIR VII, 2005
35
▲
To prevent (deterministic) detrimental
tissue effects
▲
To limit the probability of stochastic
effects to levels deemed to be acceptable
36
Effects of Cell Death
Deterministic Effects
Radiation effects for which generally a threshold
level of dose exists above which the severity of
the effect is greater for a higher dose.
Probability of Death
100%
Stochastic Effects
Radiation effects, generally occurring without a
threshold level of dose, whose probability is proportional
to the dose and whose severity is independent of the dose.
Dose
(mGy)
D
Co-60 Radiotherapy
Overexposure
Panama 2000-2001
38
37
Radiation Syndromes
Radiation-induced
Cardiovascular Disease
(Whole Body Exposures)
Acute
Chronic
Threshold: 0.5 Gy (3-7 days)
Death: 1 Gy, 2-3 Gy with medical care
6 Gy (6-9 days)
> 50 Gy
BMS
(hematopoyetic
system)
GIS
(gastro
intestinal
system)
Annual
radiation
exposures
exceeding
0.7 - 1.0 Gy and
cumulative
doses > 2-3 Gy
over 2-3 years
▲
▲
▲
LD50/60 (Acute)
CNS
(central
nervous
system)
3.3 to 4.5 Gy no medical management
Radiotherapy – well documented side
effect of irradiation for breast cancer,
Hodgkin’s disease, and peptic ulcer.
A-bomb data – statistically significant
dose-related incidence.
Chernobyl – some evidence in the
Russian study on emergency workers for
a dose-related increase.
6 to 7 Gy with medical management
Dose
39
40
Excess Relative Risk of Heart Disease
CVD vs Radiation Dose
▲
▲
▲
The Adult Health Study (AHS) of A-bomb survivors
showed a linear relationship between radiation dose and
mortality from myocardial infarction more than 40 years
after exposure, with an excess relative risk (ERR) of 0.17
(90% CI = 0.01 to 0.36) per Sievert.
The Life Span Study (LSS) of A-bomb survivors revealed
an ERR for death from heart disease of 0.14 (90% CI =
0.05 to 0.22) per Sievert.
For patients with peptic ulcer given local radiotherapy to
the stomach including partial irradiation of the heart, the
ERR increased from 0 to nearly 0.5 as the average dose to
the heart increased from 1 Gy to nearly 2 Gy.
For patients given adjuvant radiotherapy for breast
cancer leading to partial irradiation of the heart, the ERR
was about 0.3 after an average effective-single dose of 1.5
Gy to the heart.
0,6
Peptic ulcer
0,5
ERR of heart disease
▲
Preston et al 2003:
heart disease ERRsv 0.17
90% cl 0.08; 0.26
p=0.001
0,4
0,3
Preston et al 2003
data from Carr et a 2005
A-bombs
0,2
0,1
0
0
0,5
1
1,5
2
2,5
3
-0,1
dose (Sv)
(Preston et al 2003: colon dose;
Carr et al: corrected mean heart dose)
41
Irradiation of Gonads
From current evidence, a judgement can be
made of a threshold acute dose of about 0.5 Gy
(or 500 mSv) for both cardiovascular disease
and cerebrovascular disease. On that basis, 0.5
Gy may lead to approximately 1% of exposed
individuals developing the disease in question,
more than 10 years after exposure. This is in
addition to the high natural incidence
(circulatory diseases account for 30-50% of all
deaths in most developed countries).
Draft ICRP on Tissue Effects. http://www.icrp.org/page.asp?id=116
42
Threshold doses for approximately 1%
incidence in morbidity
43
Draft ICRP on Tissue Effects. http://www.icrp.org/page.asp?id=116
44
Skin Injuries
Threshold doses for approximately
1% incidence in morbidity
Multiple
Coronary
Angiography
& Angioplasty
Procedures
USA, 1991
Industrial Irradiator Accident
El Salvador, 1989
Spain, 1998
45
Draft ICRP on Tissue Effects
Draft ICRP on Tissue Effects. http://www.icrp.org/page.asp?id=116
46
Eye Injuries
Opacities
Cataracts
Di Paola, Bianchi, Baarli: Rad Res 73, 340 (1978)
47
48
Increased Risk of Cortical and Posterior
Subcapsular Cataract Formation
▲
▲
▲
▲
▲
▲
▲
Cataracts among Chernobyl Clean-Up Workers
Reanalysis of Atomic Bomb Survivors
A Cohort Of Patients With Chronic Exposure to
Low-dose-rate Radiation
From Cobalt-60 Contaminated Steel in their
Residences
Studies of Children Exposed to Low Doses from
the Chernobyl (Ukraine) Accident
Chernobyl Clean-up Workers
Commercial Airline Pilots
Space Astronauts
49
Radiation Research 167, 233-243 (2007)
50
Dose Limits – ICRP 1991, 2007
Threshold doses for approximately
1% incidence in morbidity
For occupational exposure of workers over the
age of 18 years



An effective dose of 20 mSv per year averaged over
five consecutive years (100 mSv in 5 years), and of
50 mSv in any single year;
An equivalent dose to the lens of the eye of 150 mSv
in a year;
An equivalent dose to the extremities (hands and
feet) or the skin of 500 mSv in a year
For apprentices (16-18 years of age)

Draft ICRP on Tissue Effects. http://www.icrp.org/page.asp?id=116
51
effective dose of 6mSv in a year.
52
Evolution of Limitation of Exposure
Dose Limits – ICRP 2011



Log of recommended Annual Dose in mSv/y
For occupational exposure of workers over the
age of 18 years
An effective dose of 20 mSv per year averaged over
five consecutive years (100 mSv in 5 years), and of
50 mSv in any single year;
An equivalent dose to the lens of the eye of 20 mSv
in a year;
An equivalent dose to the extremities (hands and
feet) or the skin of 500 mSv in a year
For apprentices (16-18 years of age)

Tolerance
(avoid deterministic harm)
1000
Dose limits
(minimize stochastic harm)
?
?
100
??
?
10
Workers
1st propos.1922
Population
1
introduced 1977
0.1
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000
Year
Note, for the times indicated by a ? no recommendations existed
Also units have been approximately converted from those used earlier.
effective dose of 6mSv in a year.
53
Courtesy J. Hendry
54
Deterministic Effects
Radiation effects for which generally a threshold
level of dose exists above which the severity of
the effect is greater for a higher dose.
Stochastic Effects
Radiation effects, generally occurring without a
threshold level of dose, whose probability is proportional
to the dose and whose severity is independent of the dose.
Cancer
Stochastic
Effects of
Ionizing
Radiation
Heritable Effects
55
http://rpop.iaea.org/
56
Frequency of leukemia (cases/1 million)
Thyroid cancer diagnosed up to 1998 among
children 0-17 years at the time of the Chernobyl
accident
300
Number
250
200
Belarus
Russian Federation
150
Ukraine
Total 1800
100
50
0
1990 1991 1992 1993 1994 1995 1996 1997 1998
Year
Equivalent dose (mSv)
http://rpop.iaea.org/
57
What happens at the low-dose end of the graph?
http://rpop.iaea.org/
58
Dose and Dose-Rate
Effectiveness Factor (DDREF)
a) Linear extrapolation
A judged factor that generalizes the usually
lower biological effectiveness [per unit of dose]
of radiation exposures at low doses and low
dose rates as compared with exposures at high
doses and high dose rates)
b) Threshold dose
c) Lower risk per
dose for low doses
d) Higher risk per dose
for for low doses
ICRP is taking a value of 2 for the DDREF
For radiation protection purposes, ICRP has chosen
a), acknowledging that below 100 mSv or 0.1 Gy no
deleterious effects have been detected in humans.
BEIR VII chose a value of 1.5
59
60
Scale of Radiation Exposures
ICRP Detriment-Adjusted Nominal
Risk Coefficient for Cancer
(10-2 Sv-1 – Percent per Sievert)
Exposed
Population
ICRP 103 (2007)
Cancer Induction
ICRP 60 (1991)
Cancer Fatality
Bone scan
CT scan
Typical
Radiotherapy
Fraction
Annual
Background
Whole
5.5
6.0
Adult
4.1
4.8
61
There is evidence of:
▲
62
Genetic (Heritable) Effects
(Mutations)
Genetic Susceptibility to Cancer
▲
http://rpop.iaea.org/
Fruit Fly
Experiments
Single gene human genetic disorders, where
excess spontaneous cancer is expressed in a
high proportion of gene carriers – the so-called
high penetrance genes which can be strongly
expressed as excess cancer
Variant genes of lower penetrance through
gene-gene and gene-environment interactions
can result in a highly variable expression of
cancer following radiation exposure
10
Frequency (%)
5
0
63
10
20
30
Absorbed dose (Gy)
40
64
▲
▲
Genetic Effects
HERITABLE EFFECTS
Ionizing radiation is known to cause hereditary
mutations in many plants and animals
should not be confused with
BUT
EFFECTS FOLLOWING
Intensive studies of 70,000 offspring of the atomic
bomb survivors have failed to identify an increase
in congenital anomalies, cancer, chromosome
aberrations in circulating lymphocytes or
mutational blood protein changes.
IRRADIATION IN UTERO
some of which are deterministic;
some, stochastic
65
Principles of Radiation Protection
IRRADIATION IN UTERO
ICRP 103 (2007)
End Point
Period
PreImplantation
Major
Malformations
Organogenesis
Severe Mental
8 - 15 Weeks
Retardations Post-Conception
In Utero
Cancer Risk
Exposure
Death
66
General
Dose
Threshold
Normal
incidence in
live-born
100 mGy
---
100 mGy
1 in 17
300 mGy
1 in 200
None*
1 in 1000
Medical Exposure
Justification of Practices
benefit to the exposed
individuals or to society to
outweigh the radiation
detriment?
benefits and risks of available
alternative techniques that do
not involve ionizing radiation?
Dose Limitation
for occupational and public
exposure
not applicable to medical
exposure
Optimization of Protection
ALARA
* Lifetime cancer risk ~ 3 times that of the population as whole
67
dose minimum necessary to
achieve the required diagnostic
or therapeutic objective
68