Early Effects of Radiation

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Acute Radiation Lethality
• Acute Radiation Syndrome (ARS), or radiation sickness, occurs in
humans after whole-body reception of large doses of ionizing
radiation delivered over a short period.

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Acute Radiation Lethality
• Prodromal Period
 This immediate response of radiation sickness is the prodromal period.
 At radiation doses above approximately 1 Gy (100 rad) delivered to the total
t

body, signs and symptoms of radiation sickness may appear within minutes
to hours.
 The symptoms of early radiation sickness most often take the form of
nausea, vomiting, diarrhea, and a reduction in the white blood cells of the
peripheral blood (leukopenia).

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Acute Radiation Lethality
• Latent Period
 After the period of initial radiation sickness, a period of apparent well-being
occurs.
 The time after exposure during which there is no sign of radiation sickness.
 The latent period extends from hours or less (at doses in excess of 50 Gy) tot

weeks (at doses from 1 to 5 Gy). t

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Acute Radiation Lethality
• Hematopoietic Syndrome
 Bone Marrow Syndrome
 Radiation doses in the range of
approximately 2 to 10 Gyt (200–1000 rad)
 Characterized by a reduction in white
blood cells, red blood cells, and platelets.

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Acute Radiation Lethality
• Hematopoietic Syndrome
 Prodromal: Mild symptoms; appear in a matter of a few hours and may
persist for several days.
 Latent: Can extend as long as 4 weeks; no obvious signs of illness, although
the number of cells in the peripheral blood declines during this time.
 Manifest Illness: Possible vomiting, mild diarrhea, malaise, lethargy, and
fever; each of the types of blood cells follows a rather characteristic pattern
of cell depletion.

 Death occurs because of generalized infection, electrolyte imbalance, and

dehydration.

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Acute Radiation Lethality
• Gastrointestinal (GI) syndrome.
 Radiation doses of approximately 10 to 50 Gy t

(1000–5000 rad)
 Intestinal cells are normally in a rapid state of
proliferation and are continuously being replaced
by new cells.

 When the intestinal lining is completely denuded

of functional cells, fluids pass uncontrollably
across the intestinal membrane, electrolyte
balance is destroyed, and conditions promote
infection
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Acute Radiation Lethality
• Gastrointestinal (GI) syndrome.
 Prodromal: Vomiting and diarrhea occur within hours of exposure and persist
for hours to as long as a day.
 Latent: 3 to 5 days
 Manifest Illness: A second wave of nausea and vomiting followed by
diarrhea; a loss of appetite (anorexia) and may become lethargic; diarrhea
persists and becomes more severe, leading to loose and then watery and
bloody stools.

 Death occurs principally because of severe damage to the cells lining the
intestines.

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Acute Radiation Lethality
• Central Nervous System
 Radiation dose in excess of approximately 50 Gyt(5000 rad) or higher.
 Prodromal: Excessive nervousness, confusion, severe nausea, vomiting,
diarrhea, loss of vision, burning sensation of the skin, loss of consciousness.
 Latent Period: Lasts up to 12 hours.
 Manifest Illness: Person becomes disoriented; loses muscle coordination;
has difficulty breathing; may go into convulsive seizures; experiences loss of
equilibrium, ataxia, and lethargy; lapses into a coma; and dies.

 The ultimate cause of death in CNS syndrome is elevated fluid content of the
brain.

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LD50/60
• The LD50/60 is the whole body
radiation dose that causes 50% of
irradiated subjects to die within 60
days.
• Acute radiation lethality follows a
nonlinear, threshold dose-
response relationship.

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Local Tissue Damage
• Effects on the Skin
 Basal cells are the stem cells that
mature as they migrate to the
surface of the epidermis.
 Damage to basal cells results in
the earliest manifestation of
radiation injury to the skin.

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Local Tissue Damage
• Effects on the Skin
 Follow a nonlinear, threshold dose-
response relationship.
 Small doses of x-radiation do not
cause erythema.
 Extremely high doses of x-radiation
cause erythema in all persons so
irradiated.

 The skin erythema dose required

to affect 50% of those irradiated
(SED50) is about 5 Gy (500 rad).
t

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Local Tissue Damage
• Effects on the Male Gonads
 100 mGyt (10 rad) = reduce the number of spermatozoa
 2 Gyt (200 rad) = temporary infertility; commences approximately 2 months
after irradiation and persists for up to 12 months.
 5 Gyt (500 rad) = permanent sterility.

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Local Tissue Damage
• Effects on the Female Gonads
 100 mGyt (10 rad) = may delay or suppress menstruation in a mature female
 2 Gyt (200 rad) = temporary infertility.
 5 Gyt (500 rad) = permanent sterility.

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Hematologic Effects
• Before the introduction of personnel radiation monitors, periodic
blood examination was the only monitoring performed on x-ray and
radium workers.
• This examination included total cell counts and a white blood cell
(leukocyte) differential count.

• Under no circumstances is a periodic blood examination

recommended as a feature of any current radiation protection
program.

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Hematologic Effects
• Hemopoietic System
 Consists of bone marrow, circulating
blood, and lymphoid tissue.
 Lymphoid tissues are the lymph nodes,
spleen, and thymus.

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Hematologic Effects
• Hemopoietic Cell Survival
 The principal response of the
hemopoietic system to
radiation exposure is a
decrease in the numbers of all
types of blood cells in the
circulating peripheral blood.
 Lethal injury to the stem cells
causes depletion of these
mature circulating cells.

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Cytogenetic Effects
• Cytogenetics
 Defined as the study of cell genetics with an emphasis on cell chromosomes.
• Karyotype
 Chromosome map

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Cytogenetic Effects
• Single-Hit Chromosome
Aberrations
 The breakage of a chromatid is called
chromatid deletion.

 During S phase, both the remaining

chromosome and the deletion are
replicated.

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Cytogenetic Effects
• Single-Hit Chromosome
Aberrations
 The chromosome aberration visualized at
metaphase consists of a chromosome
with material missing from the ends of two
sister chromatids and two acentric
(without a centromere) fragments.
 These fragments are called
isochromatids

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Cytogenetic Effects
• Multi-Hit Chromosome
Aberrations
 In the G1 phase of the cell cycle, ring
chromosomes are produced if the
two hits occur on the same
chromosome.
 Dicentrics are produced when
adjacent chromosomes each sustain
one hit and recombine.

21
Cytogenetic Effects
• Multi-Hit Chromosome Aberrations
 Reciprocal translocations are multi-hit chromosome aberrations that require
karyotypic analysis for detection.
 Radiation-induced reciprocal translocations result in no loss of genetic
material, simply a rearrangement of the genes.

22
Cytogenetic Effects
• Kinetics of Chromosome
Aberration
 At very low doses of radiation, only
single-hit aberrations occur.

 When the radiation dose exceeds

approximately 1 Gyt(100 rad), the
frequency of multi-hit aberrations
increases more rapidly

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Cytogenetic Effects
• Kinetics of Chromosome
Aberration
 Single-hit aberrations are produced
with a linear, nonthreshold dose-
response relationship

 Multihit aberrations are produced

following a nonlinear,
nonthreshold relationship

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Late Effects of Radiation

25
Local Tissue Effects
• Skin
 Early radiologists who performed fluoroscopic examinations without
protective gloves developed a very callused, discolored, and weathered
appearance to the skin of their hands and forearms.
 In addition, the skin would be very tight and brittle and sometimes would
severely crack or flake.

 This stochastic effect was observed many years ago in radiologists and is
called radiodermatitis

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Local Tissue Effects
• Cataracts
 A cloudy area in the lens of your eye
 The dose-response relationship for
radiationinduced cataracts is nonlinear,
threshold.

 Most investigators would suggest that

the threshold after an acute x-ray
exposure is approximately 2 Gyt(200
rad).

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Local Tissue Effects
• Cataracts
 Both the National Council on Radiation Protection and
Measurements (NCRP) and the International Commission on
Radiological Protection (ICRP) have categorized a
radiationinduced cataract as a “deterministic effect.”

 A threshold (2 Gyt) in dose below which the effect does not occur.
 The severity of the effect increases with dose above the
threshold.
 The effect is thought to be caused by damage to many cells.
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Life Span Shortening
• Radiation-induced life span shortening
is nonspecific, that is, no characteristic
diseases are associated with it, and it
does not include late malignant effects.
• It occurs simply as accelerated
premature aging and death.

• At worst, humans can expect a reduced

life span of approximately 10 days for
every 10 mGyt.

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Risk Estimates
• Relative Risk
 Computed by comparing the number of persons in the exposed population
showing a given stochastic effect with the number in an unexposed
population who show the same stochastic effect.

• Excess Risk
 The difference between the observed number of cases and the expected
number

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Risk Estimates
• Absolute Risk
 Consists of units of cases/ population/dose.
 If at least two different dose levels are known

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Risk Estimates
• Absolute Risk Question
 The absolute risk for radiation-induced breast cancer is 5 × 10−2 Sv− for a 20-
year at-risk period (actually it’s much less than this). If 100,000 women
receive 1 mSv during mammography, how many fatal cancers would be
expected to be induced?

 There are approximately 300,000 American radiologic technologists, and

they receive an annual effective dose of 0.5 mSv (50 mrem). What is the
expected number of annual deaths because of this occupational exposure?

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Radiation Induced Malignancy
• Leukemia
 A number of human population groups
have exhibited an elevated incidence
of leukemia after radiation exposure—
atomic bomb survivors, American
radiologists, radiotherapy patients, and
children irradiated in utero, to name a
few.

 Acute leukemia and chronic myelocytic

leukemia were observed most often
among atomic bomb survivors
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Radiation Induced Malignancy
• Thyroid Cancer
 Shown to develop in three groups of patients whose thyroid glands were
irradiated in childhood.
 The Ann Arbor series and the Rochester series.
 21 children who were natives of the Rongelap Atoll in 1954

• Bone Cancer
 Radium watchdial painters.
 Patients treated with radium salts for a variety of diseases, from arthritis to
tuberculosis.

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Radiation Induced Malignancy
• Skin Cancer
 Induced in radiation therapy recipients treated with orthovoltage (200 to 300
kVp) or superficial x-rays (50 to 150 kVp).
 Radiation-induced skin cancer follows a threshold dose-response
relationship.

• Breast Cancer
 Tuberculosis patients
 Radiation treatment of benign postpartum mastitis
 Atomic bomb survivors

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Radiation Induced Malignancy
• Lung Cancer
 Workers in the Bohemian pitchblende mines of Germany
 American uranium miners

• Liver Cancer
 Patients injected with the contrast agent Thorotrast.

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Radiation and Pregnancy
• Irradiation in Utero
 The effects of radiation in utero
are time related and radiation
dose related
 All observations point to the first
trimester during pregnancy as
the most radiosensitive period

37
Radiation and Pregnancy
• Irradiation in Utero
 The first 2 weeks of pregnancy may be
of least concern because the response
is all-or-nothing.

 Either a radiation-induced abortion

occurs, or the pregnancy is carried to
term with no ill effect.

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Radiation and Pregnancy
• Irradiation in Utero
 During the period of major
organogenesis, from the 2nd through
the 12th weeks, two effects may occur.

 Early in this period, skeletal and organ

abnormalities can be induced.
 As major organogenesis continues,
congenital abnormalities of the central
nervous system may be observed if the
pregnancy is carried to term.

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Radiation and Pregnancy
• Irradiation in Utero
 A dose of 100 mGyt(10 rad) during
organogenesis is expected to increase
the incidence of congenital
abnormalities by 1% above the natural
incidence

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Radiation and Pregnancy
• Irradiation in Utero
 Irradiation in utero at the human level has been associated with childhood
malignancy by a number of investigators.
 Although the Oxford Survey has reviewed all malignancies, it is the findings
of radiation-induced leukemia that have been of particular importance.

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Genetic (Hereditary) Effects

42
Genetic (Hereditary) Effects
• Cause of Genetic Mutations
 Biologic effects of ionizing radiation on
future generations are termed genetic,
or hereditary, effects.
 They can occur as a result of
radiationinduced damage to the DNA
molecule in the sperm or ova of an
adult, leading to germ cell mutations.
 These cause faulty genetic
information to be transmitted to the
offspring

43
Genetic (Hereditary) Effects
• Natural Spontaneous Mutations
 Some mutations in genetic material occur
spontaneously, without a known cause.
 Hemophilia
 Huntington's chorea
 Down syndrome (mongolism)
 Duchenne's muscular dystrophy
 Sickle cell anemia
 Cystic fibrosis
 Hydrocephalus.

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Genetic (Hereditary) Effects
• Ionizing Radiation as a Possible
Cause of Genetic (Hereditary) Effects
 The only concrete evidence showing that
ionizing radiation causes genetic effects
comes from extensive experimentation with
fruit flies and mice at high radiation doses

 We do not have any data that suggest that

radiation-induced genetic effects occur in
humans.

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Genetic (Hereditary) Effects
• Doubling Dose Concept
 The radiation dose that causes the number of spontaneous mutations
occurring in a given generation to increase to two times their original number.

 For example, if 7% of the offspring in each generation are born with

mutations in the absence of radiation other than background levels, the
administration of the doubling dose to all members of the population would
eventually increase the number of mutations to 14%

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References
• Bushong. Radiologic Science for Technologist: Physics, Biology,
and Protection 11th Ed
• Sherer, et al. Radiation Protection in Medical Radiography 8th Ed
• Bushberg, et al. The Essential Physics of Medical Imaging 3rd Ed
• Hall and Giaccia. Radiobiology for Radiologist 8th Ed

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