Late Effects of Radiation

Prepared by: Me
Late effects of radiation (Stochastic effect) –

radiation response is not observed for months or

years
incidence of the radiation response increases with

increasing radiation dose

Early effects are produced by high radiation dose

Late effects are a result of low doses delivered over a long

period of time

Radiation induced malignancy and genetic effects

Life shortening and local tissue damage

 Radiation protection guides are based on the late effects of
radiation and on linear, nonthreshold dose-response
relationships

Diagnostic radiology – low dose and low LET

Radiation induced malignancy and genetic effects

Late effects – stochastic effects

Increasing incidence of response-not severity- with increasing

dose
Local tissue effects
Skin

Erythema, desquamation, late-

developing carcinoma
Early radiologists (fluoroscopy) –

callused, discolored, and

weathered appearance to the skin
of the hands and forearms
 Skin would be very tight and

brittle and sometimes would

severely crack or flake
 Radiodermatitis – radiation
burn
 Dose to produce such effects is

very high
 No such effects in current
practice of Radiology
Chromosomes

Chromosome damage in circulating lymphocytes

Can continue to show for as long as 20 years

(peripheral stem cells)

Chromosome damage in the circulating lymphocytes can

be produced as both a deterministic and a stochastic

response
Cataracts

Cyclotron – developed by E.O. Lawrence in 1932

Cyclotron physicist used radiographic IS to locate high

energy beams.
1949 - cataracts in cyclotron physicists (radiation
induced)
Radiosensitivity of the eye is age dependent

Latent period – 5-30 years

Neutron and proton radiation - has high LET, high

RBE for production of cataracts
If dose to the lens exceeds 1000 rad, cataracts develop

in nearly 100% of those who are irradiated

CT - 5 rad per slice
 Radiation induced cataracts occur on the posterior
pole of the lens

Dose response relationship of radiation induce cataracts is

nonlinear, threshold
 Radiologic technology is a safe occupation

Life-span shortening
Linear, nonthreshold

Average life-shortening caused by occupational accidents

amounts to 74 days, for radiation workers, life is shortened

by only 12 days
Radiation induced life span shortening is nonspecific – no

characteristic disease are associated with it, and it does not

include late malignant effects.
Accelerated premature aging and death

No life span shortening has been observed among atomic

bomb survivors
Radium watch-dial painters, x-ray patients, and other

radiation exposed populations has not been reported

At worst, humans can expect a reduced life span of

approximately 10 days for every rad
 Risk of life span shortening as a consequence of occupation, disease, or various other conditions

Risky condition Expected days of life lost

Being male rather than female 2800
Heart disease 2100
Being unmarried 2000
One pack of cigarettes a day 1600
Working as a coal miner 1100
Cancer 980
30 pounds overweight 900
Stroke 20
All accidents 435
Service in Vietnam 400
Motor vehicle accidents 200
Average occupational accidents 74
Speed limit increase from 55 to 65 40
Radiation worker 12
Airplane crashes 1
Risk estimates
Three types: relative, excess, absolute

Relative risk
 Observation of large population for late effects of radiation

without having any knowledge of the radiation dose

 Comparison of the number of persons in the exposed
population showing a given late effect with the number in an
unexposed population who show the same effect
Relative risk = 1.0 – no risk

Relative risk = 1.5 – 50% higher in the irradiated population

Radiation hormesis suggest that low levels of radiation-less

than approximately 10 rad (100 mGy) - are good for you

Protective effect by stimulating molecular repair and

immunologic response mechanisms

Relative risk of less than 1 is the hormetic region

The theory of radiation hormesis suggests that very low

radiation doses are beneficial
Excess risk

The difference between the observed number of cases

and the expected number

Excess cases is assumed to be radiation induced.
Absolute risk

If two different dose levels are known

Consists of units of cases/population/dose

Linear, nonthreshold dose relationship

Radiation induced malignancy
Leukemia
Incidence increases with increasing radiation dose
Atomic bomb survivors

Radiation induced leukemia follows a linear, nonthreshold

dose-response relationship

Radiation induced leukemia is considered to have a latent

period of 4 to 7 years and at risk period of approximately 20
years
 Summary of the incidence of leukemia in atomic bomb
survivors

Hiroshima Nagasaki Total

Total number 74,456 25,037 99,393

of survivors in
study

Observed cases 102 42 144 of leukemia

Expected cases 39 13 52 of leukemia

Radiologists
Anemia and leukemia

Doses of 100 rad/year

Patients with ankylosing spondylitis

High doses if radiation to the spinal column (Rad.
Thera.)
Leukemia
Dose to bone marrow = 100 to 4000 rad
Cancer
Ionizing Radiation
can cause cancer
Thyroid cancer
Ann Arbor series and the
Rochester series (1940s and
1950s) – treatment for thymic
enlargement
 500 rad dose
 20 years later – thyroid nodules and
cancer began to appear
21 children native of the Rongelap Atoll (1954)
 High levels of fallout during a hydrogen bomb test
 1200 rad dose
Bone Cancer
Radium watch painters – most often
female workers; watch dials laden with
radium sulfate;
 Radium were ingested through tongue touch
of the brush;
 Radium salts emit alpha and beta particles

 Currently – tritium (3H) and promethium

(147Pm)
 Behaves like calcium and deposit in bones

 Half-life of radium = 1620; alpha emission

radiation doses to bone is up to 50,000 rad
Skin Cancer
Begins with development of

radiodermatitis
Orthovoltage treatment -200 to 300 kVp

Superficial x-rays - 50 to 150 kVp

Latent period of approximately 5 to 10

years
Radiation induced skin cancer follows a nonlinear, threshold
dose-response relationship
Breast cancer

Patients with tuberculosis

under treatment
Acute postpartum mastitis

– 75 to 1000 rad
Lung cancer

Bohemian pitchblende mines

of Germany
 Radon exposure contributed to
the incidence of lung cancer
American uranium miners

High concentration of uranium ore

Half-life of uranium = 109 years; decays through a series of

radioactive nuclides by successive alpha and beta emissions,

each accompanied by gamma emission

Radon (222Rn): decay product of uranium

Can deposit in the lungs and decay to stable isotope of lead

Liver cancer
Thorotrast (Thorium dioxide) colloidal suspension contrast agent for

angiography
Latent period of 15 to 20 years

ThO2 particles are deposited in phagocytic cells of reticuloendothelial

system and are concentrated in the liver and spleen

Radiation and Pregnancy
During pregnancy, concern is directed to possible congenital
effects in newborns

Effects on fertility
100 rad per year, no noticeable depression in fertility is
noted

Low-dose chronic irradiation does not impair fertility

Irradiation in utero
 Within 2 weeks of fertilization, the most pronounced effect of

radiation is prenatal death (spontaneous abortion)

 Major organogenesis – 2 nd through 12th week – skeletal and

organ abnormalities can be induced

 If radiation induced abnormalities are severe enough, the

result will be neonatal death

 Does of 10 rad during organogenesis – increase incidence of

congenital abnormalities by 1%
All observations point to the first trimester during pregnancy
as the most radiosensitive period

Radiation in utero does not retard growth and

development; it has been associated with microcepahly
and mental retardation
Radioiodine – concentrates on the thyroid

 Thyroid begins to functions at 10 weeks of gestation

 The first two weeks of pregnancy may be of least concern
because the response is all or nothing

The relative risk of childhood leukemia after irradiation in

utero is 1.5
 Summary of effects after 10 rad in utero
Time of exposure Type of response Natural Radiation response
occurrence
0-2 wk Spontaneous 25% 0.1%
abortion
2-10 wk Congenital 5% 1%
abnormalities
2-15 wk Mental retardation 6% 0.5%

0-9 mo Malignant disease 8/10,000 12/10,000

0-9 mo Impaired growth 1% Nil

0-9 mo Genetic mutation 10% Nil

 We do not have any data that suggests that radiation-induced
genetic effects occur in humans

Genetic effects
Genetic effects studies have come from large scale experiments

with flies or mice

Atomic bomb survivors – no radiation-induced genetic effects

H.J. Muller – (Drosophila) fruit fly

Russel - mice
Doubling dose in humans is estimated to lie in the range

between 50 and 250 rad

Incidence of radiation-induced genetic mutations after the

levels of exposure experienced in diagnostic radiology is

essentially zero

The doubling dose is that dose of radiation that produces

twice the frequency of genetic mutations as would have been
observed without the radiation
The prefertilized egg, in its various stages, exhibits a constant

sensitivity to radiation; however it also demonstrated some

capacity for repair of genetic damage. If repair occurs, it is
rapid; therefore a delay in procreation of only a few days may
be appropriate
In male, it might be prudent to refrain from procreation for a

period of 60 days to allow cells that were in a resistant stage

of development at that time of exposure to mature to
functioning spermatids
SUMMARY
LINEAR-NONTHRESHOLD DOSE-
RESPONSE RELATIONSHIP
No level of radiation is completely safe and the degree of

response is directly proportional to the amount of

radiation received.
This effect is the basis for all radiation protection

standards.
LINEAR-THRESHOLD DOSE-RESPONSE RELATIONSHIP

A dose of radiation must reach a certain dose threshold

for a response to occur. No response exists if the dose

threshold is not met
NONLINEAR-THRESHOLD DOSE-RESPONSE
RELATIONSHIP.

A safe ('threshold') dose of radiation exists that, when

exceeded, results in responses that are not directly

proportional to the dose received
NONLINEAR-NONTHRESHOLD DOSE-RESPONSE
RELATIONSHIP

No level of radiation is completely safe and the degree of

response is not directly proportional to the dose received.

LINEAR QUADRATIC, NONTHRESHOLD DOSE
RESPONSE

Risks associated with low dose levels of low LET radiation

Stochastic somatic and genetic effects

Leukemia, breast cancer and heritable damage assume

this curve
 Deterministic effect Stochastic effects
Nonstochastic effect Late effect
Early effect

Radiation response occurs within Radiation response is not observed for

minutes or days after exposure months or years

Effects of radiation that become more Randomly occurring effects of radiation;

SEVERE at high levels of radiation the PROBABILITY of such effects is
exposure and do not occur below a PROPORTIONAL to the DOSE
certain threshold dose (increased dose equals increased
probability, not severity of effects)

response increases in severity with incidence of the radiation response

increasing radiation dose increases with increasing radiation dose

Nonlinear, threshold dose response Linear, nonthreshold dose-response

At very high LET, cell survival kinetics follow the single-target,
single-hit model

With low LET radiation, the multitarget, single-hit model

applies

Radiation protection guides are based on the late effects of

radiation and on linear, nonthreshold dose-response
relationships
Skin effects from high-dose fluoroscopy follow a sigmoid-type
dose-response relationship

Radiation induced leukemia follows a linear, nonthreshold

dose-response relationship

Radiation-induced cancer, leukemia, and genetic effects

follow a linear-nonthreshold dose-response relationship
Single-hit Chromosome aberrations – linear, nonthreshold
dose response relationship

Multi-hit chromosome aberrations – non-linear,

nonthreshold

Radiation-induced chromosome aberrations follow a

nonthreshold dose response relationship

Life span shortening - Linear, nonthreshold

 Dose response relationship of radiation induce cataracts is
nonlinear, threshold

Acute radiation lethality follows a non-linear, threshold

dose-relationship

Radiation induced skin cancer follows a nonlinear, threshold

dose-response relationship