Radiation Biology Q

1
Radiation Biology Q A

• Robert L. Metzger, Ph.D.

2
Radiobiology QA

• How far does the average photon in an x-ray beam
  go before experiencing a collision?

3
Radiobiology QA

• One Mean Free Path.
• MFP 1/?
• The mean free path is the distance the average
  photon travels before making a collision.

4
Radiobiology QA

• Does the spacing between collisions of
  monochromatic photons increase as a beam with
  good geometry penetrates tissue?

5
Radiobiology QA

• Yes. The linear attenuation coefficient does not
  change appreciably with tissue depth, but the
  number of available photons does. If fewer
  photons survive, then the spacing between
  collisions must increase.

6
Radiobiology QA

• What is the range of a beam of 100 keV electrons
  in soft tissue, give that the average LET is 1
  keV/?m?

7
Radiobiology QA

• 100 keV maximum range x 1 keV/?m.
• So the max range is 0.1 mm.

8
Radiobiology QA

• Nine Gray of 250 kVp x-rays will kill 99 of the
  hamster fibroblast cellsin a petri dish. A 0.45
  Gy dose of another radiation will do the same.
  What is the RBE of the second radiation?

9
Radiobiology QA

• RBE is the energy required to produce a given
  effect (e.g.cell killing), as compared to 250 kVp
  x-rays.
• So 9 Gy/0.45 20
• It must be an alpha particle.

10
Radiobiology QA
X-ray produced chromosomal aberrations, such as
dicentrics and rings, are generated as a
consequence of
A. A single chromosomal break interacting with
itself. B. Interaction of two separate
chromosomal breaks. C. Two single strand breaks
on the same chromosome. D. Misreplication events
11
Radiobiology QA
This option is correct. The justification for
this answer is a follows Chromosomal aberrations
that are generally lethal to the cell, result
from the illegitimate recombination of double
strand breaks in two chromosomes. A dicentric, as
its name implies, has two centromeres, one from
each of two separate chromosomes. It is
impossible to get a complex aberration such as a
dicentric or a ring from one chromosome break
(hence option A is incorrect) as a result of
misreplication events (hence option D is
incorrect). Single strand breaks are readily
repaired, unless there are breaks on opposite
strands close together. Even when it would result
only in one double strand break, it is not enough
to produce an exchange type aberration
12
Radiobiology QA
For how long after a total body exposure of 1 Gy
do detectable chromosomal aberrations persist in
peripheral lymphocytes?
A.Days B.Weeks C.Months D.Years
13
Radiobiology QA
You answered D After a total body exposure of 1
Gy detectable chromosomal aberrations persist in
peripheral lymphocytes for years. This option is
correct. The justification for this answer is as
follows Some chromosomal aberrations are
potentially lethal, causing the cell to die when
the cell attempts to divide (so called unstable
aberrations). This includes, for example, a
dicentric. Consequently, these aberrations are
removed slowly over a long period of time, but it
takes many years for them to disappear from human
peripheral lymphocytes. Other chromosomal
aberrations are commensurate with cell viability
(so called stable aberrations). This includes
symmetrical translocations, which are not removed
over time since they do not cause a cell to die
in attempting to divide. These aberrations can be
detected by chromosome painting, i.e.,
fluorescent in situ hybridization, or FISH. Both
dicentrics and translocations can still be
detected in the A-bomb survivors who were exposed
over 50 years ago, though the number of
dicentrics has now decreased.
14
Radiobiology QA

• A cell is considered to have retained its
  reproductive integrity following exposure to
  radiation, if
• DNA replication has occurred
• It has undergone two mitoses
• It is intact and functioning
• It has produced a colony of 60 cells.

15
Radiobiology QA

• For a given total dose of x rays, a protracted
  exposure at low dose rate is less effective in
  killing mammalian cells than an acute exposure at
  high dose rate, primarily because
• Fewer free radicals are produced
• The mitotic cell cycle is shortened
• Ion pairs recombine during extended exposure
• Repair of sublethal damage occurs during exposure

16
Radiobiology QA
A protracted exposure allows more opportunity for
the repair of sub-lethal damage, leading to a
reduction in the number of cells killed by a
given total dose. As for the other options The
number of free radicals produced depends on the
dose, not in the time over which it is delivered
(dose rate), so that option A is
incorrect. Radiation tends to lengthen, rather
than shorten the cell cycle, so option B is also
incorrect.
17
Radiobiology QA

• A cell is considered to have retained its
  reproductive integrity following exposure to
  radiation, if
• It has undergone two mitoses
• DNA replication has occurred
• It is intact and functioning
• It has produced a colony of 60 cells.

18
Radiobiology QA
A cell is said to have retained its reproductive
integrity if it is capable of sustained
proliferation, i.e. if it can grow into a
macroscopic colony of perhaps 60 cells or
more. Option A is incorrect, since after two
divisions the colony would be tiny, consisting of
only 4 cells. Exposure to radiation may cause
chromosomal damage in a cell, which would cause
it to die in attempting the next or a subsequent
division damaged cells can often go through a
few divisions before they peter out. Cells
doomed to die can synthesize DNA and become a
giant cell consequently option B is
incorrect. Cells that are out of cycle can still
function after substantial doses of radiation. If
called upon to divide days or months later, they
may die because their chromosomes are damaged.
The ability to function is not, therefore, an
indication that the cell has retained its
reproductive integrity consequently option C is
incorrect.
19
Radiobiology QA

• The most radiosensitive portion of the GI tract
  to cell killing is the
• Esophagus.
• Stomach.
• Small intestine.
• Large intestine.
• Oropharynx.

20
Radiobiology QA
All of the G.I. tract is sensitive to both cell
killing and to the induction of carcinomas by
exposure to radiation. However, radiation
sensitivity varies markedly between the midpoint
and the ends the esophagus, oropharynx, and
rectum are relatively radiation-resistant, and
the midpoints, including the stomach and small
intestine, are more sensitive. The small
intestine is the most sensitive portion of the GI
tract to cell killing because of the rapidly
proliferating cells of the mucosal epithelium in
the crypts. These cells divide approximately once
every 24 hours, making this the most rapidly
proliferating tissue and one of the most
radiosensitive tissues in the body. The
relatively high sensitivity of the of the mucosal
lining compared with the underlying components
means that acute changes are of the most clinical
significance and that late changes rarely occur.
21
Radiobiology QA

• A radiologist develops a pronounced erythema of
  the hands 2 weeks after exposure. Which of the
  following is true?
• The threshold dose for an erythema is 10 Gy
• Thick lead gloves (0.5 mm Pb equivalent) would
  have prevented 90 of the dose.
• The erythema is unlikely to be accompanied by a
  temporary epilation
• Late erythema is usually followed by necrosis

22
Radiobiology QA
Lead gloves, if they are thick, and contain a
lead equivalent of 0.5 mm, do indeed stop 90 of
the dose of diagnostic quality x rays. This
answer is therefore a true statement. Thin
flexible gloves would not be as protective. As
for the other options... The threshold dose for a
transient erythema is about 2 Gy, and for a main
erythema reaction is about 6 Gy consequently
option A is incorrect. The threshold dose for a
temporary epilation is only 3 Gy, lower than that
for the main erythema reaction which appears at
one and a half weeks post irradiation. Thus, the
pronounced main erythema seen here is likely to
be accompanied by a temporary epilation which
makes option C incorrect. On the other hand,
delayed necrosis requires a dose of about 12 Gy,
much higher than that for a late erythema, so
that option D is incorrect.
23
Radiobiology QA

• What determines the time delay between exposure
  to radiation and death in the gastrointestinal
  and hematopoietic syndromes?
• The proportion of stem cells sterilized
• The lifetime of the mature functioning cells
• The duration of the cell cycle of the stem cells
• The mitotic delay in the stem cells

24
Radiobiology QA
Both the gastrointestinal and hematopoietic
syndromes result from the failure of a
self-renewal system, the intestinal epithelium
and the circulating blood elements respectively.
In a classical self-renewal system, cells
produced by cell division in the stem cell
compartment then pass through a series of steps
to differentiate before becoming functioning
cells. Radiation kills some or all of the stem
cells, cutting off the supply of cells to
differentiate. This does not immediately
compromise the well-being of the organism since
the functioning cells are still in place. The
problem arises sometime later when the
differentiated functioning cells reach the end of
their useful life and are removed it then
becomes evident that replacements are not
available because of the damage to the stem cell
compartment. Option B is correct the life-time
of the mature functioning cells determines the
interval between exposure to radiation and the
crisis that may result in death.
25
Radiobiology QA

• Which of the following statements is true
  concerning total body irradiation of humans with
  an acute exposure to x rays?
• The LD50/60 is between 3 and 5 Gy.
• Seizures are likely if the dose exceeds 3 Gy.
• The nadir in white cell count following a dose of
  2 Gy will occur within 6 days.
• Bone marrow transplants are likely to save
  individuals exposed to more than 15 Gy.

26
Radiobiology QA
The LD50 is the lethal dose, 50, i.e., the dose
that would be lethal to half of an irradiated
population. The subscript 60, refers to death
within 60 days of exposure, indicating that it is
death due to failure of the hematopoietic system.
For a dose between 3 and 5 Gy this mode of death,
also known as bone-marrow death is expected, so
option A is correct. It is not clear that any
dose will result in seizures, certainly not below
doses commensurate with the cerebrovascular
syndrome (100 Gy), so option B is incorrect.
27
Radiobiology QA

• Transient erythema is seen as a consequence of
  exposure to a radiation dose of
• 0.25 Gy
• 0.5 Gy
• 1 Gy
• 2 Gy

28
Radiobiology QA
You answered D Transient erythema is seen as a
consequence of exposure to a radiation dose of 2
Gy. This answer is correct. The justification for
is as follows Erythema is an early reaction,
similar to sunburn, caused by vasodilation, edema
and loss of plasma constituents from
capillaries. The approximate threshold dose is 2
Gy consequently option D is correct.
29
Radiobiology QA

• Following an acute x-ray exposure of 8 Gy, which
  appears first?
• Main Erythema reaction
• Permanent epilation
• Dry desquamation
• Telangiectasia

30
Radiobiology QA
There is an ordered hierarchy in time and dose
for the skin changes that occur following
irradiation. Early transient erythema (2 to 24
hours) is followed by the main erythema reaction
(1 ½ weeks) followed by epilation (3 weeks),
desquamation (4 weeks), necrosis (gt10 weeks), and
telangiectasia (gt 52 weeks). Option A is correct
erythema is the first observable reaction of the
skin.
31
Radiobiology QA

• Concerning radiation induced heritable effects,
  which of the following statements is true?
• Radiation induced heritable changes are different
  from those that occur spontaneously.
• Humans are much more sensitive than mice.
• 10-20 of heritable changes in the population can
  be attributed to diagnostic radiation.
• The double dose in the human is estimated to be
  0.5 to 2.5 Sv (acute exposure).

32
Radiobiology QA
The best quantitative data on heritable effects
of radiation come from experiments with mice. The
doubling dose, i.e. the radiation dose required
to double the spontaneous mutation rate, was
estimated by the BEIR V committee to be in the
range 0.5 to 2.5 Sv, and by the UNSCEAR (1988)
committee to be 1 Sv. Option D is therefore the
correct answer. As for the other choices Option
A is incorrect because the heritable changes
induced by radiation are indistinguishable from
those that occur spontaneously radiation simply
increases the incidence. Data from the first
generation offspring of the A-bomb survivors
allow an estimate to be made of the doubling dose
for the human, although it is not statistically
significant. The estimated value is 1.58 Sv for
an acute dose in humans, compared with the 1 Sv
(or 0.5 to 2.5 Sv) for a protracted exposure in
mice, i.e. humans appear to be rather more
resistant than mice. Option B is therefore
incorrect. This option is incorrect because the
ICRP estimate for the risk of hereditary
disorders is 0.6 x 10-2 per Sv. The GSD from
diagnostic radiation is of the order of 300 mSv
per annum, which corresponds to be a hereditary
risk of only (0.6 x 10-2 Sv-1) x (3 x 10-4) Sv,
or 0.00018.
33
Radiobiology QA

• Which statement is true concerning
  radiation-induced sterility?
• 0.5 Gy acute dose of gamma rays can induce
  temporary sterility in males.
• 1 Gy acute dose of gamma rays or more can induce
  permanent sterility in females.
• Radiation induced permanent sterility in males
  leads to loss of libido.
• Radiation induced sterility in females does not
  produce hormonal changes.
• An acute dose of 2 Gy gamma rays will cause
  immediate sterility in males (i.e. no latent
  period).

34
Radiobiology QA
The threshold for temporary sterility in males
exposed to a single absorbed dose in the testes
is about 0.15 Gy. Option A is therefore a true
statement. As for the other options As mentioned
in the review, the threshold for permanent
sterility in women is an acute absorbed dose in
the range of 2.5 to 6 Gy. Option B is therefore
incorrect. The induction of sterility by
radiation in human males does not produce
significant changes in hormone balance, libido,
or physical capability. By contrast, pronounced
hormonal changes, comparable to those associated
with the natural menopause, accompany
radiation-induced sterilization in females.
Consequently, options C D are incorrect. The
effect of radiation on fertility is not apparent
immediately, i.e. there is a latent period,
because the postspermatogonial cells are
relatively resistant compared with the sensitive
stem cells. After exposure to a moderate dose of
radiation, the individual remains fertile as long
as mature sperm cells are available, but
decreased fertility or even temporary sterility
follows if these are used up. Option E is
therefore incorrect.
35
Radiobiology QA

• Which of the following statements is true
  concerning radiation oncogenesis?
• Generally, the mean latent period for
  radiation-induced leukemia is about 20 years.
• Children are less sensitive than adults to the
  induction of leukemia.
• Benign neoplasms are not induced after
  irradiation.
• Solid tumors induced by radiation may appear 50
  years or more after exposure.
• A whole-body dose of 0.1 Gy would be expected to
  increase the incidence of cancer from
  approximately 20 (the natural incidence) to
  approximately 30.

36
Radiobiology QA
Following exposure to whole body irradiation, an
excess incidence of leukemia shows up within a
few years, reaching a peak at 5 to 7 years
option A is therefore incorrect. By contrast to
leukemia, solid tumors take longer to show up.
However, as stated in the text, the excess risk
for carcinogenesis apparently manifests itself as
a lifelong elevation of the natural age-specific
cancer risk. In the A-bomb survivors, for
example, there is still an excess incidence of
solid tumors today, more than 50 years after the
exposure to radiation option D is therefore
correct. As for the other options, children and
teenagers are much more sensitive than adults to
radiation carcinogenesis. See figure 7 in the
review material. Option B is therefore
incorrect. Radiation induces benign as well as
malignant tumors the thyroid in children is the
best example, where benign nodules as well as
malignant tumors are common following an exposure
to radiation. Option C is also incorrect. The
risk estimate for radiation induced cancer, for
the general population (which includes children),
exposed to a single acute dose of low LET
radiation, is 10 per Sv, (or Gy). A dose of 0.1
Gy would result in a 1 incidence of cancer, not
to 10 as indicated in option E, which is
therefore incorrect.
37
Radiobiology QA

• Which of the following organs in a child is most
  sensitive to the induction of both benign and
  malignant tumors from low doses of x rays?
• Bone
• Brain
• Thyroid
• Extremities

38
Radiobiology QA
You answered C In a child the thyroid is the
most sensitive organ to the induction of both
benign and malignant tumors from low doses of  x
rays. This option is correct. The justification
is as follows Organs which contain larger
proportions of cycling cells are generally the
more radiogenic. Option C is therefore correct.
39
Radiobiology QA

• The dose response relationship for solid tumors
  in the Japanese survivors used by the BEIR V and
  UNSCEAR committees has the form _____________.
• linear no threshold
• linear with threshold
• quadratic no threshold
• exponential
• quadratic with threshold

40
Radiobiology QA
The dose response relationship for solid tumors
in the Atomic-bomb survivors, used by the
national and international committees, is linear
no threshold, i.e., the cancer incidence up to
about 2.5 Sv increases in proportion to dose.
There is no apparent threshold, i.e., there is no
dose below which the risk is zero. This, of
course, is an assumption since there are no data
at very low doses. Adding a quadratic term in
dose does not improve the fit to the data for
solid tumors, though it does for leukemia
41
Radiobiology QA

• In which age range are women least susceptible to
  radiation-induced breast cancer?
• lt 20 years
• 20-29 years
• 20-39 years
• 40-49 years
• gt 49 years

42
Radiobiology QA
For most malignancies, sensitivity to
radiation-induced cancer is greatest in children
and decreases with age. This age dependence for
radiation-induced cancer is particularly striking
for breast cancer. Young girls before the age of
10 years, and teenagers are most susceptible,
with the incidence of radiation-induced cancer
falling with age at the time of exposure.
43
Radiobiology QA

• The ICRP estimate of the total number of cases of
  cancer of all types produced by a total body
  exposure of a working population to 1 Sv of low
  LET radiation at low dose-rate is closest to
• 4 in 102
• 4 in 103
• 4 in 104
• 4 in 105

44
Radiobiology QA
The ICRP suggest risk estimates for fatal
radiation induced cancer, which vary for the
general population (including children) versus a
working population (no children below 18 years of
age), and for high dose-rate versus low
dose-rate. For the situation in this question, a
working population exposed at low dose-rate, the
risk is 4 / Sv. Option A is therefore correct.
45
Radiobiology QA

• Which of the following is considered to be a
  deterministic effect of radiation?
• Leukemia
• Opacification of the ocular lens
• Carcinoma of the prostate
• Mutation in a second generation offspring

46
Radiobiology QA
A stochastic effect is an all-or-nothing effect,
i.e., the severity of the effect does not vary
with dose, though the probability of it occurring
is dose dependent. A stochastic effect is
believed to be due to damage to one or a few
cells, and there is no threshold in dose.
Radiation induced leukemia, cancer, and
hereditary effects fall into this category. By
contrast a deterministic effect has a threshold
in dose, and above this threshold the severity of
the effect increases with dose. It is believed to
be due to damage to many cells. A Cataract, i.e.
an opacity of the ocular lens, falls into this
category. Option B is therefore correct
47
Radiobiology QA

• The minimum single acute dose of x rays that will
  result in a cataract is closest to
• 0.5 Gy
• 1.0 Gy
• 2.0 Gy
• 4.0 Gy

48
Radiobiology QA

• An acute exposure of 1 Gy to the embryo/fetus at
  1 week gestation age is most likely to result in
• Congenital anomalies
• Microcephaly
• Embryonic death
• Mental retardation

49
Radiobiology QA
Gestation is divided into preimplantation,
organogenesis, and the fetal period. In humans,
these periods correspond to about 0 through 9
days, 10 days through 6 weeks, and 6 weeks
through term, respectively. Irradiation during
preimplantation leads to death of the embryo.
Growth retardation or malformations are generally
not seen in animals at this time. The human data
are consistent with this conclusion. In humans,
mental retardation is one of the most important
endpoints observed, but this is typically not
observed before 7 weeks gestation, and reaches a
peak at 8 to 15 weeks. Consequently, option C is
correct.
50
Radiobiology QA

• The most likely consequence of an acute radiation
  dose of 0.5 Gy during the 8 to 15 week gestation
  period is
• Fetal death
• Mental retardation
• Childhood malignancy
• Congenital heart disease

51
Radiobiology QA
8 to 15 weeks represents the most radiosensitive
period for the induction of severe mental
retardation by radiation. The estimated risk is
approximately linear with dose at 40 /Sv. The
risk for 0.5 Gy is therefore 20 by far the
largest risk of the four presented. Option B is
correct. As for the other options... During the
fetal period, the fetus is relatively resistant
to killing by radiation, so that 0.5 Gy would be
unlikely to result in fetal death. Option A is
therefore incorrect. The risk of a childhood
malignancy is about 6 / Sv, so that the risk
halved would be about 3 for 0.5 Gy i.e., much
lower than for mental retardation. Consequently,
option C is incorrect. Since 0.5 Gy is much too
low to induce congenital heart disease, option D
is also incorrect.
52
Radiobiology QA

• Based on the data from the A-bomb survivors, for
  irradiation during weeks 8-15 of gestation, the
  risk of serious mental retardation is closest to
• 1 per Gy
• 4 per Gy
• 10 per Gy
• 40 per Gy

53
Radiobiology QA
The incidence of severe mental retardation as a
function of dose is reported to be apparently
linear without threshold at 8 to 15 weeks, with a
risk coefficient of 0.4 per Gy (0.4-100 rad). The
data are also consistent with a dose threshold of
0.12 to 0.2 Gy (12-20 rad). The incidence is
about four times lower at 16 to 25 weeks. Option
D is therefore correct.
54
Radiobiology QA

• A worker in a nuclear medicine laboratory
  declares that she is 3 months pregnant. What is
  the NCRP dose limit for the remainder of the
  pregnancy?
• None
• 0.05 mSv/month
• 0.5 mSv/month
• 3 mSv total
• 30 mSv total

55
Radiobiology QA
Once a pregnancy is declared, the maximum
permissible dose to the fetus is 0.5 mSv (0.05
rem) per month. Until a pregnancy is declared, no
special limits apply to the mother other than
those applicable to any radiation worker. Option
C is correct. Once a pregnancy is declared, the
duties of a radiation worker should be reviewed
to ensure that this limit is not exceeded.