Download RAD 114 RADIATION PROTECTION CELL RADIOSENSITIVITY

RAD 114 RADIATION
PROTECTION
RADIATION BIOLOGY, PART II
CELL RADIOSENSITIVITY
In addition to the type of radiation
as having an impact on cell
radiosensitivity, the presence of
oxygen in tissues also plays an
important role. In general,
oxygenated cells are more
sensitive to radiation than hypoxic
cells.
CELL RADIOSENSITIVITY
One way to relate the degree to which
oxygen affects cell radiosensitivity is
the OXYGEN ENHANCEMENT
RATIO (OER). It is the ratio of the
dose required to affect a response
under hypoxic conditions to the dose
required to affect the same response
under oxygenated conditions.
OER =
Dose Under Hypoxic Conditions
Dose Under Oxygenated Conditions
LAW OF BERGONIE &
TRIBONDEAU
At the turn of the century,
two French scientists
determined that cell
radiosensitivity depended
on three things...
CELL RADIOSENSITIVITY
INCREASES AS...
• DIFFERENTIATION DECREASES
• REPRODUCTIVE ACTIVITY
INCREASES
• THE MITOTIC HISTORY
INCREASES (NUMBER OF
DIVISIONS OVER THE COURSE OF
THE CELL’S LIFE)
CELL RADIOSENSITIVITY
If cells are highly specialized
such as a neuron
neuron,
radiosensitivity is less than if
cells are non-specialized such
as neuroblasts.
CELL RADIOSENSITIVITY
Cells which proliferate rapidly are more
sensitive to radiation than those cells
which do not. Since lymphocytes live
for a very short time (~24 hours) they
must be replaced rapidly to maintain
immune system health. These are the
most sensitive blood cells in the body.
CELL RADIOSENSITIVITY
Cells with relatively long
mitotic histories ((over the
course of a cell’s lifetime) are
more sensitive to radiation
damage than those whose
histories are relatively short.
RELATIVE CELL
RADIOSENSITIVITY
•
•
•
•
LYMPHOCITES
EPITHELIAL TISSUES
MUSCLE TISSUE
NERVE TISSUE
RELATIVE CELL
RADIOSENSITIVITY
Reproductive cells vary in their degree
of radiosensitivity with the immature
cells being more sensitive than the
mature cells. Female reproductive
cell radiosensitivity declines from
birth until about 20 or 30 years.
ORGANIC EFFECTS
Organic effects of radiation are
those that can be observed at
the macroscopic level
level. These
have been observed in insects,
animals and human beings
(atomic bomb and nuclear
reactor victims).
TWO MAIN TYPES:
• EARLY SOMATIC EFFECTS
• LATE SOMATIC EFFECTS
ORGANIC EFFECTS
Early somatic effects are
seen early on following
exposure to radiation
and are the result of
acute high-dose
radiation exposure.
TYPES OF EARLY EFFECTS
•
•
•
•
•
NAUSEA
FATIGUE
SKIN REDDENING
EPILATION
DESQUAMATION
EARLY EFFECTS
One or more of the early effects
outlined may appear following
radiation therapy treatments.
However, the area of the body
exposed is small (compared to
whole-body exposures).
Consequently, the effects are
localized.
EARLY EFFECTS
When a large dose is delivered to
the whole body, the early effects
are more severe and may occur
in succession. The manifestation
of these effects is called ACUTE
RADIATION SYNDROME.
ACUTE RADIATION
SYNDROME
•
•
•
•
PRODROME
LATENT PERIOD
MANIFEST ILLNESS
RECOVERY OR DEATH
ACUTE RADIATION
SYNDROME
• HEMATOPOIETIC EFFECTS
• GASTROINTESTINAL EFFECTS
• CEREBROVASCULAR EFFECTS
HEMATOPOIETIC EFFECTS
Due to the relative radiosensitivity of
cells in the body, the bloodforming organs are primarily
affected. Above 100 rad, chances
of survival diminish with increasing
dose. Recovery may occur in
weeks or months.
GASTROINTESTINAL
EFFECTS
At doses from 600 rad to 1000 rad,
in addition to blood-forming organ
effects, the digestive system is
also effected. Death occurs in
days as the epithelial cells are
destroyed, causing bleeding,
infection and dehydration.
CEREBROVASCULAR
EFFECTS
At doses of 5000 rad or more, death
occurs within hours or days due to
p and
cardiovascular collapse
neurological impairment. Given the
extent of radiation dose, the victim
does not have time to exhibit
hematopoietic or gastrointestinal
effects (thankfully!).
LATE SOMATIC EFFECTS
Are the result of either wholey or partial bodyy doses
body
of radiation given acutely or
over a long period. They
manifest themselves
months or years later.
MAJOR TYPES OF LATE
EFFECTS
• STOCHASTIC EFFECTS:
CARCINOGENESIS
BIRTH DEFECTS (TERATOGENESIS)
• NONSTOCHASTIC EFFECTS:
CATARACTOGENESIS
FIBROSIS
STERILITY
NON-SPECIFIC LIFE SPAN SHORTENING
CANCER RISK
The result of exposure to high
doses of radiation over long
periods is well documented.
E l radiology
Early
di l
pioneers
i
such
h
as Clarence Dally and uranium
dial painters were painful
reminders of the dangers of
ionizing radiation.
CANCER RISK
Low-dose effects cannot be
directly known. Cancer risk is
extrapolated from high dose
“extrapolated”
data obtained from atomic
bomb survivors. Consequently,
any dose is assumed to be
potentially carcinogenic.
CANCER RISK
A report from the National
Academy of Sciences called
BEIR V
V,” concluded that
“BEIR
except for leukemia, the risk
of cancer followed a linear,
non-threshold dose-response
relationship.
CANCER RISK
Still, it is believed that the risk of
cancer is outweighed by the
benefit that radiological
g
studies
provide. This does not excuse
carelessness in the use of
ionizing radiation by
technologists.
BIRTH DEFECTS
It is a well-known fact that unborn are
highly susceptible to ionizing
radiation during
g the first trimester of
pregnancy. Therefore, unless a lifeor-death situation is involved, women
should not have elective radiological
procedures during the first three
months of pregnancy.
CATARACTOGENESIS
It can be shown that a single
dose of 200 rad given to the
eyes will induce cataracts. The
relationship between radiation
dose and cataractogenesis
follows a threshold, non-linear
pattern.
LIFE SPAN SHORTENING
Long-term exposure can, if
unchecked, lead to non-specific life
span shortening. Recent studies of
radiologists
di l i t h
have shown
h
th
that,
t
compared to other medical
specialists, the average life span
appears to be the same. This was
not true 50 years ago.
GENETIC EFFECTS
These are effects in
reproductive cells BEFORE
fertilization Normally
fertilization.
Normally, a
genetic defect is recessive
unless the defect is present
in both parents.
GENETIC DEFECTS
Radiation-induced genetic defects
have not been clearly demonstrated
in humans. However, this does not
mean that they do not occur.
Therefore, it is important that not only
the occupationally exposed, but the
population as a whole limit exposure
to ionizing radiation.
DOUBLING DOSE CONCEPT
The dose that, when received by
an entire population,
population would result in
a doubling of the natural incidence
of mutations. It is believed to be
around 156 rem.
GENETICALLY SIGNIFICANT
DOSE CONCEPT
The average gonadal dose that
takes into account the number of
people in a population and the
expected contribution of children.
GENETICALLY SIGNIFICANT
DOSE CONCEPT
It assumes that if every member of
the population received the same
dose of radiation (above normal
background levels) it would have the
same genetic effect as a few
individuals receiving a proportionally
larger dose.
GENETICALLY SIGNIFICANT
DOSE CONCEPT
For example, the genetic effect of
100,000 people each receiving 12
mrad would be identical to 10,000
people each receiving 120 mrad.
GENETICALLY SIGNIFICANT
DOSE CONCEPT
This concept also assumes
th t radiation-induced
that
di ti i d
d genetic
ti
mutations are cumulative and
that any dose is potentially
mutagenic.
RISK ESTIMATES
Scientists can estimate the
amount of radiation-induced
cancer risk
i k on th
the b
basis
i off
three measures, each of
which depends on specific
kinds of data.
RISK ESTIMATES
• RELATIVE RISK
• EXCESS RISK
• ABSOLUTE RISK
RELATIVE RISK
In the absence of precise dose
data, relative risk is calculated
as the ratio of observed cases
of cancer to the number of
expected cases (in the absence
of radiation).
RELATIVE RISK
For example, if 12 cancer
cases are observed in a
population
l ti off 20
20,250,
250 yett th
the
expected cases of cancer in a
population of 100,000 is 45,
what is the relative risk?
RELATIVE RISK
Expected Cases = 45 ÷ 105 = 0.00045
0.00045 • 20,250 = 9.1125
Observed Cases = 12
Relative Risk =
12
= 1.32
9.1125
EXCESS RISK
A measure of radiation-induced
cancer risk based on the number
of observed cases that exceed
expected cases. Using the
previous example, the excess
risk is 12-9=3 cases.
ABSOLUTE RISK
Using specific dose data, absolute
risk is calculated as:
• Number of Expected Cases per
million population, multiplied
by
• Dose in RAD
ABSOLUTE RISK
The incidence of cancer deaths in
the population is 10 per million per
rad per year. What is the
expected rate of cancer deaths
among the 300,000 American
radiographers if they receive an
annual effective dose equivalent
of 8 mrad?
ABSOLUTE RISK
Cancer Deaths = 10 ÷ 10 6 = 0 . 00001
0 . 00001 • 300 , 000 = 3
Absolute Risk = 3 • 0.008 =
0.024 cases/yr