Interaction of Radiation with Biological
Matter:
(what is biological dose?)
Bill McBride
Division of Cellular and Molecular Oncology
Dept. Radiation Oncology
David Geffen School Medicine
UCLA, Los Angeles, Ca.
wmcbride@mednet.ucla.edu
Room B3-109, x47051
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Objectives:
– Know the characteristics of ionizing radiation
that make it useful for RT
– Define LET and RBE and what is meant by
quality of radiation
– Know the difference between direct and indirect
action of radiation and the role of free radicals
– Recognize the impact of oxygen on initial
radiation damage and of hypoxia in tumor RT
– Understand how biological radiation dose and
physical radiation dose differ
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Radiation Therapy
• Approximately 50% of cancer patients
receive RT with curative intent
• Approximately half of these are cured
Radiation Therapy has a long history!
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Roentgen with his wife’s hand,
1895
X-rays were rapidly
adapted for use as a
clinical treatment,
initially for noncancerous conditions,
but soon for cancer, as
well.
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FIRST CURE OF CANCER BY X-RAYS
1899 - BASAL CELL CARCINOMA
X-rays were used to cure cancer very soon after their discovery
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And rapidly became a standard treatment
Hammersmith Hospital, London, 1905
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Although side-effects were
encountered!
This is a picture of a 70 year old
person who was irradiated by
Freund at the of age 5 in Austria
1896 for nevus pigmentosus
piliferus.
L. Freund, Ein mit Rontgenstrahlen behandelter
fall von nevus pigmentosus piliferus. Wein. Med.
Wochschr. 47, 428-434 (1987).
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Initially more non-cancerous diseases were
treated that cancer (still popular in Europe)
Lupus
Epilepsy
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The Nobel Prize in Physiology or Medicine 1946
"for the discovery of the production of mutations by means of X-ray irradiation
However, its use for benign
conditions has been limited
in most countries for fear of
radiation-induced cancer.
The carcinogenic effects of
X-rays was discovered
using fruit flies by Muller in
1946.
Hermann J. Muller
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Natural radioactivity was discovered by Becquerel, who was awarded the Nobel
Prize in Physics in 1903 along with Marie and Pierre Curie "in recognition of the
extraordinary services they have rendered by their joint researches on the
radiation phenomena"
Henri Becquerel
Marie Curie
Maltese cross
“One wraps a Lumiere photographic plate with a bromide emulsion in two sheets of very thick black paper, such that the plate does not become
clouded upon being exposed to the sun for a day. One places on the sheet of paper, on the outside, a slab of the phosphorescent substance, and
one exposes the whole to the sun for several hours. When one then develops the photographic plate, one recognizes that the silhouette of the
phosphorescent substance appears in black on the negative. If one places between the phosphorescent substance and the paper a piece of
money or a metal screen pierced with a cut-out design, one sees the image of these objects appear on the negative. One must conclude from
these experiments that the phosphorescent substance in question emits rays which pass through the opaque paper and reduces silver salts.”
Paris 1896
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Natural Radioactivity
  particles
– Positively charged, helium nucleus
  particles
– Negatively charged, electrons
 -rays
– No charge, EMR
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Radioisotopes also were soon being used to
treat and cure cancer.
First cure of
cancer by
radium plaque 1922
Radioactive
plaques and
implants are still in
common use, for
example in prostate
implant seeds.
Radium applicators were used for
many other conditions!
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Therapeutic Benefit and R.T.
There is always a need to derive a therapeutic
benefit from RT. There are 2 main ways by
which this is achieved:
1. Physical means
– distributing dose by treatment planning
2. Biological means
– dose fractionation
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1-25 MeV
500 KeV
150 KeV
50 KeV
20 KeV
Megavoltage
Orthovoltage
Superficial Therapy
Contact Therapy
Grenz Rays
Major improvements in RT
during the mid-1900s came
from improved penumbra
and decreased skin dose
associated with higher
energy x-rays, cobalt, and
high energy photons.
More recently conformal
RT, IMRT, IGRT,
Gammaknife, Cyberknife,
tomotherapy, SRS, SRT,
protons, heavy ions, etc.
have added considerable
variety to the choices for
physical radiation delivery
and present radiobiological
challenges.
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History of Fractionation
1896 Freund - treated hairy nevus with fractionated doses
1900 Stenbeck - cured skin cancer with single doses
1906 Bergonie and Trubandeau introduced the “Law” that radiosensitivity is related
to cell proliferation (NOT TRUE!) to explain why fractionated doses sterilized
rams without skin reactions
Regaud - treated uterine cancer with fractionated doses
1914 Schwartz
- Fractionation is superior because of cell cycle redistribution
1919 Coutard cures deep-seated H&N tumors
1932 Coutard shows fractionation superior to single dose
1944 Strandquist - empirical laws for changing dose per fraction
1967 Ellis - Nominal Standard Dose (NSD) formula
1980s Linear Quadratic formula gains favor
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The First Radiation Dosimeter!
Early x-ray machines took a long time to deliver effective dose and
gave skin reactions that could be circumvented by dose fractionation.
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From Amaldi and Kraft, “Radiotherapy with beams of carbon ions, Reports on Progress in Physics, 68, (2005)
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History has repeatedly shown that dose fractionation
results in a therapeutic advantage
“In order to save machine time, a 3-day-a-week schedule was
initiated in 1962. This schedule was quickly abandoned in preoperative irradiation because of increased wound healing problems.
Although acute reactions in the 3-day-a-week schedule for protracted
radical irradiation were not excessive, late radiation sequelae are
probably more pronounced as observed 2 or more years later.”
Fletcher, 1966.
3 x 3.3 Gy
5 x 2 Gy
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Clinical RT is Changing, which Presents
Challenges and Opportunities for Radiobiology
Conventional treatment:
Tumors are irradiated to a specified dose with 2Gy fractions delivered, more or less
homogeneously, in a 6 week time period
• Varying this schedule impacts outcome
• Radiobiological modeling attempts to provide guidelines for customization of RT using
– Radiobiological principles derived from preclinical data
– Radiobiological parameters derived from clinical altered fractionation protocols
Modern treatment:
IMRT etc allows optimized non-homogeneous dose distributions, concomitant boosts,
dose painting - dose heterogeneity
SRS, SRT, HDR, Protons, Heavy Ions - high dose/fx issues
Molecular and chemical targeting - dose adjustment
Molecular prognosis and diagnosis promise individualized treatment plans and biological
treatment planning
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• Radiobiology has derived means of
understanding why dose fractionation gives a
therapeutic benefit.
• New physical delivery methods need to
incorporate and/or modify these concepts.
• In order to understand either conventional or
newer treatment effects, one needs to know
the differences between physical and
biological radiation dose
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What is Radiation?
• Radiation is classified into two main categories:
- Non-ionizing radiation
- Ionizing radiation
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ELECTROMAGNETIC RADIATIONS
 (cms)
10-9
10-8
10-7
E (eV) 1.24x107
10-6
10-5
10-4
10-3
10-2
1
10
102
103
1.24x102
Radar
Microwaves
 rays
U.V.
IONIZING
RADIATION
104
1.24x10-13
v
i
s
i
b
l
e
X-rays
10-1
Infra Red
T.V.
Radio
Short Waves
Radio Waves
NON-IONIZING RADIATION
Photon E = h(energy = Planck’s const x frequency)
= hc/ (c = speed of light,  = wave length)
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• Non-ionizing radiation
– Is a particle or wave that has enough kinetic energy to raise the
thermal energy of an outer shell electron and cause excitation
with emission of low energy EMR (infrared)
• Ionizing radiation
excitation
and ionization
 particle
excitation
ionization
-ray
’ray
– Ionizing radiation has enough kinetic energy to detach at least one electron from an
atom or molecule, creating ions
– Charged particles such as electrons, protons, heavy ions, alpha and beta particles are
directly ionizing because they can interact directly with atomic electrons through
coulombic forces and transfer a major part of their kinetic energy directly
– In contrast, photons (x rays,  rays) and neutrons are chargeless and therefore more
penetrating. They are indirectly ionizing. They have sufficient kinetic energy to free an
orbital electron producing a ‘fast’ recoil or Compton electron that is, in turn, directly
ionizing
• Energy is deposited in “packets”, which is why, when it is deposited in DNA, ionizing radiation is
an efficient cytotoxic agent
• Ionizing radiation has an energy in excess of 124 eV, which corresponds to a  < about 10-6 cm.
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Ionization produces ions, ion radicals, and free radicals concentrated
along tracks and especially at Bragg peak of primary and secondary
electrons. They are highly reactive and cause damage to biological
matter
SECS
10-18
10-16
10-14
10-12
Ion formation – H2O+ and e-
Absorption of energy
Excitation and H and OH radical formation
Physical effects
ION RADICAL LIFETIME
Chemical lesions
10-6
FREE RADICAL LIFETIME
100
BREAKAGE OF BONDS
CHEMICAL REPAIR / MISREPAIR
ENZYMIC REPAIR / MISREPAIR
Chemical repair
Enzyme repair/lesion
Mins-Hrs
EARLY BIOLOGICAL EFFECTS
Hrs-Days
Days-Years
106
LATE BIOLOGICAL EFFECTS
Cellular effects
Tissue effects
Systemic effects
• Ion - atom or molecule that has lost an electron and is charged.
• Free radical - atom or group of atoms that contains an unpaired electron and is highly reactive
• Aqueous electron - has lost kinetic energy and has been captured by water - a powerful reducing agent.
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The Gray is the Physical Unit of
Radiation
•
•
1 GRAY, the unit of absorbed dose (1 joule / Kg),
– Causes 1-2 x 105 ionization events / cell
– 1% in DNA
– A single cobalt 60 ray will deposit about 1mGy in a cell
Rad (Radiation Absorbed Dose) is the old unit = cGy
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Direct and Indirect Action of Radiation
• Indirectly ionizing radiation can act directly or
indirectly on biological targets
• If the ion pairs and free radicals are produced in a
biologic target (DNA) then this is direct action
• If water or other atoms or molecules are ionized,
diffusible free radicals can act as intermediaries to
cause damage - this is indirect action
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Direct and Indirect Action of Ionizing
Radiation on DNA
4 nm
photon
H2O
OH
.
e-
p+
INDIRECT ACTION
photon
R.
ep+
2 nm
DIRECT ACTION
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Reactive Oxygen Species (ROS)
• Since H2O is the major component in cells, the most common
ionization event is radiolysis of water, producing reactive oxygen
species (ROS)
• The most relevant water is within 2nm of the DNA and tightly bound
• ROS produced include: H. - reducing; OH. - oxidizing; HO2. - oxidizing
(O2 + H.); H2O2 - oxidizing
• The net effect is oxidation of cellular constituents
• About 60% of DNA damage caused by x-rays is due to ROS
• About 75% of the indirect action of radiation is due to hydroxyl radicals
(OH.)
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Free OH. radicals generate organic radicals by:
– Addition
– Hydrogen abstraction
– Electron transfer
R + OH.
RH + OH.
R + OH.
.ROH
R . + H 2O
R. + OH -
Where R is the organic moiety
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Free Radicals and their Scavengers
Matter
•
•
•
Biological effects of ionizing radiation are determined in large part by free
radicals
Free radicals are involved in many biological processes, including cellular
respiration
We have defenses against free radicals
– Endogenous free radical scavengers - most relevant within 2nm of the DNA
– Anti-oxidants
• eg superoxide dismutase, especially in mitochondria, and catalase
•
Free radical scavengers can protect normal tissue from radiation
– eg Amifostine
•
•
Depleting free radical scavengers will radiosensitize
What interacts with free radicals, in particular radicals in biological
materials will be important in determining outcome at this level
• Oxygen interacts with free radicals
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Oxygen Matters
• Binds H radicals forming hydrogen peroxide
H . + O2
HO2. (+HO2. )
H2O2 (+O2)
• Binds electrons to give superoxide
e- + O2
O2- + (H2O)
•
HO2. + OH-
Binds organic radicals to form peroxides
R . + O2
RO2. (radical peroxide)
RO2. + R’ H
ROOH + R’ (hydroperoxide)
RO2. + R’.
ROOR’ (peroxide)
Oxygen “fixes” the radical lesions in DNA in a form that can not
be easily chemically repaired and therefore is a very powerful
radiosensitizer.
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Oxygen Enhancement Ratio (OER)
=
Dose required to produce a specific biological effect in the absence of oxygen
Dose required for the same effect in its presence
OER varies with level of effect but can be 2.5 - 3 fold
1) Culture Cells
4) irradiate under oxic or hypoxic conditions
5) Plate cells and
grow for about 12 days
0 Gy
2) Suspend Cells
( trysinization)
2Gy 4Gy
.. . ..
. ..
6Gy
6) Count colonies
1.0
S.F.
3) Count cells in hemocytometer
Physical Dose = Biological Dose
hypoxic
oxic
0.1
0.01
0
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2
4
6
Dose (Gy)
8
10
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Clinical Relevance of Hypoxia
The effects of hypoxia were first
discovered in 1909 by Schwarz who
showed that strapping a radium source on
the arm gave less of a skin reaction than
just placing it there. This was used to give
higher doses to deep seated tumors.
Giacca and Brown
Pimonizadole (oxygen mimetic)
staining colorectal carcinoma
• Hypoxic areas occur almost solely in tumors and are more
radioresistant than oxic areas.
• Hypoxia contributes to treatment failure
• Reoxygenation occurs between radiation dose fractions giving a
rationale for dose fractionation
• The oxygen effect is greater for low LET than high LET radiation
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RADIATION QUALITY AND
BIOLOGICAL EFFECTIVENESS
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LINEAR ENERGY TRANSFER
Separation of ion clusters in relation to
size of biological target
LOW LET
Radiation
gamma rays
deep therapy
X-rays
soft X-rays
alpha-particle
LET is average energy (dE) imparted by excitation
and Ionization events caused by a charged particle
traveling a set distance (dl) - LET = dE/dl (keV/ m)
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HIGH LET
Radiation
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• A dose of 1 Gy will give 2x103
ionization events in 10-10 g (the size
of a cell nucleus). This can be
achieved by:
excitation and ionization
– 1MeV electrons
•700 electrons which give 6
ionization events per m.
– 30 keV electrons
 particle
•140 electrons which give 30
ionization events per m.
– 4 MeV protons
•14 protons which give 300
ionization events per m.
excitation
ionization
-ray
’-ray
• The biological effectiveness of
these different radiations vary!
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Relative Biological Effectiveness
(RBE) of the Radiation Matters
=
Dose of 250 kVp x-rays required to produce an effect
Dose of test radiation required for the same effect
1.0
0.1
S.F.
0.01
Low LET, HDR
High LET
0.001
DOSE Gy
Physical Dose = Biological Dose
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RBE and OER as a function of LET
8
4
Fast
Neutrons
6
Alpha
Particles
RBE
(for cell kill)
overkill
4
RBE
2
0
3
Co-60 Diagnostic
gamma rays X-rays
0.1
1
10
OER
100
OER
2
1
1000 0
Linear Energy Transfer (LET keV/m)
OER is the inverse of RBE because OER depends considerably on the
indirect action of ionizing radiation
RBE is maximal when the average distance between ionization events =
distance between DNA strands = 2nm
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DNA is the Primary, but not the only, Cellular
Target for Radiation
• Microbeam irradiation of cell cytoplasm
does not generally cause cell death, but
irradiation of the nucleus does
• Tritiated thymidine incorporated into cells
can kill them
• Radiation-induced chromosomal
abnormalities correlate with cell death
and carcinogenesis
• However, irradiation of the cytoplasm is
not without biological consequences
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The lesions in DNA that are associated with cell death
and carcinogenesis after radiation exposure are large
OH . eaqu
OH . eaqu
OH . eaqu
Lesion size
about 15-20
nucleotides
OH . eaquv
OH . eaqu
OH . eaqu
OH . eaqu OH . e
OH . eaqu aqu
OH . eaqu
OH . eaqu
OH . eaqu
OH . eaqu
Spur
4 nm diam
3 ion pairs
100 eV energy
95% of energy deposition events
Blob
7 nm diam.
12 ion pairs
The high cytotoxic efficiency of ionizing radiation can be ascribed
to the deposition of low levels of energy in small packets within
the DNA that cause lesions large enough to be fatal
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DOUBLE STRAND BREAK
30/ CELL / GRAY
SINGLE STRAND BREAK
1000 / CELL / GRAY
INTRASTRAND
CROSSLINK
0.5 / CELL / GRAY
BASE CHANGE (eg C - U)
BASE LOSS
INTERSTRAND
CROSSLINK
1000 / CELL / GRAY
*
DNA-PROTEIN
CROSSLINK
1 / CELL / GRAY
BASE MODIFICATION
(eg thymine/cytosine glycol)
SUGAR DAMAGE
(abstraction of hydrogen atom)
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• Not all ionization events are lethal!!
• As a rough guide the fraction of cells surviving 2Gy
(SF2Gy) is about 0.5
• If the S.F. 2Gy is 0.5, what is the S.F. after 60Gy?
= 0.530 = 0.9x10-9
• If the S.F. 2Gy is 0.7, what is the S.F. after 60Gy?
= 0.730 = 2.2x10-5
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What is the Lethal Lesion?
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X- or -radiation is sparsely ionizing; most damage can be
repaired
4 nm
Repairable Sublethal Damage
2 nm
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It is hypothesized that the lethal
lesions are large double strand
breaks with Multiply Damaged
Sites (MDS) that can not be
repaired. They are more likely to
occur at the end of a track
4 nm
Unrepairable Multiply Damaged Site
2 nm
Single lethal hit
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At high dose, intertrack
repairable Sublethal Damage may
Accumulate forming
unrepairable, lethal MDS
Also known as  - type killing
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Dose Rate Matters
1.0
Low Dose Rate
0.1
allows continuous SLDR
S.F.
0.01
Low LET, HDR
0.001
DOSE Gy
Physical Dose = Biological Dose
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Chromatin Structure Matters
•
•
•
•
•
Each cell contains about 2m of DNA
The basic structure is the nucleosome, which is 146 base
pairs of DNA wrapped around 2 copies of histones H2A,
H2B, H3, and H4
Nucleosomes are in turn wrapped around other proteins to
form compacted chromatin
Chromatin is maximally compacted during mitosis
Transcription requires decompaction to facilitate initiation
(binding of transcription factors and RNAP II) and
elongation
miniband
- 30nm
840nm
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Chromatin Structure and Radiation
Responses
• Compact chromatin is more radiosensitive than non-compacted
–Mitotic cells
• are 2.8 times more sensitive to DNA breaks than interphase cells
• have a lower OER (eg 2.0 compared with 2.8)
• do not have much of a “shoulder” on their survival curve
–Actively transcribing genes are less sensitive to damage
• Decompaction and compaction require acetylation and deacetylation of
histones by acetyltransferases (HAT) and deacetylases (HDAC)
• HDAC inhibitors are entering the clinic as anti-cancer agents and can radiosensitize
• Radiation Damage to DNA is not randomly distributed.
1
• It varies with cell cycle phase and level of gene expression S.F.
LATE S
.1
EARLY S
Physical Dose = Biological Dose
.01
0
G1 PHASE
G2/M PHASE
4
8
12
Dose (Gy)
16
20
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700R
1500R
Withers, H. R. and Elkind, M. M. Radiology 91:998, 1968
Used the macrocolony assay in mouse
jejunum to assessed the effects of 2
radiation doses given varying times apart
to measure the time to and extent of repair,
redistribution, and repopulation
(regeneration) between dose fractions.
Repopulation
Redistribution
12.5Gy
14.0Gy
15.5Gy
17.0Gy
Repair
Colony derived from a
single surviving clonogen
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Tissue Type Matters
ACUTE RESPONDING TISSUES
(responses seen during standard therapy)
Gut
Skin
Bone Marrow
Mucosa
LATE RESPONDING TISSUES
1
Surviving
Fraction
Acute Responding
Tissues and
Many Tumors
.1
(responses seen after end of therapy)
Brain
Spinal Cord
Kidney
Lung
Bladder
Late Responding
Tissues
.01
0
4
8
12
16
20
Dose (Gy)
Physical Dose = Biological Dose
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Dose Fractionation
1
Surviving
Fraction
Fractionated dose
Late responding tissues
.1
Fractionated dose
Acute responding tissues
Single dose
Late responding tissues
Single dose
Acute responding tissues
.01
0
4
8
12
16
20
24
Dose (Gy)
Dose fractionation spares late responding tissues more than acute
responding tissues and many tumors
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The Aim is to Increase Therapeutic
Benefit!
1.0
Probability
of tumor
control/
of normal
tissue
damage
therapeutic benefit
0
A B
Dose (Gy)
C
Normal tissue complication dose-response curves are steep!
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Biological effectiveness of RT varies with
•
•
•
•
•
•
•
•
•
•
Size of Dose (D) - (alpha and beta)
Size of Dose Per Fraction (d) - (alpha and beta)
Time over which it is delivered (T)- (alpha and beta)
Time between fractions (t)
Volume irradiated (V)
Quality of Radiation (Q) - RBE
Presence/Absence of Oxygen - OER
DNA Repair efficiency and completeness
Cell cycle phase and level of gene activation
Tissue/Tumor Type
Physical Dose = Biological Dose
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4Rs OF RADIOBIOLOGY RELEVANT TO
CLINICAL DOSE FRACTIONATION
• Repair of sublethal damage
- spares late responding normal tissue preferentially
• Reassortment/Redistribution of cells in the cell cycle
– increases acute effects
– no influence on late effects
– increases damage to tumor
• Repopulation/Regeneration
– spares acute responding normal tissue preferentially
– no influence on late effects,
– danger of tumor repopulation
• Reoxygenation
– no influence on normal tissue responses
– increases tumor damage
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Questions on
Interaction of Radiation with Biological Matter:
what is biological dose?
Bill McBride
Dept. Radiation Oncology
David Geffen School Medicine
UCLA, Los Angeles, Ca.
wmcbride@mednet.ucla.edu
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1. The lifetime of radicals in target molecules is
about
– 10-3 secs
– 10-6 secs
– 10-9 secs
– 10-12 secs
#2 – free radicals are highly unstable and reactive
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2. Electromagnetic radiation is considered ionizing
if it has a photon energy greater than
– 1.24 eV
– 12.4 eV
– 124 eV
– 1.24 keV
#3 – this is sufficient to break bonds in biological
molecules
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3. The S.I. unit of absorbed dose is
– Becquerel
– Sievert
– Gray
– Roentgen
#3 The International System (IS) unit is the Gray, named
after the radiobiologist Louis “Hal” Gray who was based
in London
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4. Which of the following are not charged
particles?
– Electrons
– Neutrons
– Protons
– Heavy ions
– Alpha particles
#2 – which is why they are called NEUTRons
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5. Which of the following is NOT a characteristic of the
indirect action of ionizing radiation
– Production of diffusible free radicals
– Production of reactive oxygen species
– Involvement of anti-oxidant defenses
– Causes a change in redox within a cell favoring
reduction of constituents
#4 the free radicals produced makes ionizing
radiation an oxidative stress overall
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6. Which of the following is true about the oxygen
enhancement ratio
– Is the same at all levels of cell survival
– Can be measured by the dog-leg in a cell survival
curve after single high dose irradiation of tumors
– Is the ratio of doses needed for an isoeffect in the
absence to the presence of oxygen
– Is low for cells in S cell cycle phase compared to
cells in G2/M phase
#3 responses should be compared by the doses
needed for a particular isoeffect. The OER varies with
the level of effect eg survival
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7. Which of the following is true about Linear Energy
Transfer
– It is a measure of the biological effectiveness of
ionizing radiation
– Shows an inverse correlation with the oxygen
enhancement ratio
– Is maximal at a relative biological effectiveness of
150 keV/micrometer
– Is measured in keV/micrometer
#4 LET is an average value imparted per unit path length.
Because the radiations vary in energy, the LET is not
biologically very useful
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8. The Relative Biological Effectiveness of a
radiation is
– Assessed by the dose required for to
produce the same effect as 250kVp X-rays
– Is the ratio of the dose required of 250 kVp
X-rays to that of the test radiation for a given
isoeffect
– Is directly related to Linear Energy Transfer
– Is about 3 for alpha particle radiation
#2 - again, measured by isoeffective doses – classically
relative to 250kVp x-rays, but often more recently 60Co
has been used
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9. The lethal lesion caused in DNA by low LET
ionizing radiation is
– 15-20 nucleotides in size
– Caused by alpha-type events
– Does not correlate with chromosomal
aberrations
– Due to oxygen fixation
#1 The lesions are large i.e they are not point mutations.
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10. Approximately how many DNA double
strand breaks are caused per cell per Gray?
– 1-10
– 15-25
– 30-40
– 45-60
– 60-75
#3 This probably varies considerably depending on
numerous factors, but this is a reasonable approximation
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11.
If the fraction of cells surviving 2Gy irradiation is
0.5, what is a reasonable estimate of the percent of
DNA double strand breaks that are effectively
repaired?
– 99%
– 95%
– 75%
– 50%
#1 If 60-80 DSB/2Gy kills half the cells, then >99% must
be repaired
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12. If the fraction of cells surviving 2Gy is 0.4,
what is the surviving fraction after 50 Gy
given in 2Gy fractions?
– 10-8
– 10-9
– 10-10
– 10-11
#3 - 0.425 = 1.12x10-10
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13. Sublethal DNA damage is most likely to
accumulate
– At high total doses given at high dose rate
– At high total doses under hypoxia
– After high LET radiation
– After low fractionated doses of radiation
#1 Intertrack interactions between ionization events are
more likely at high dose and high dose rate
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15. Sublethal DNA damage is most likely to be repaired
– After high total doses given at high dose rate
– If cells are held in a non-proliferative state
– After high LET radiation
– Between low fractionated doses of radiation
#4 The lower the number of ionization events in time and
space, the more likely they are to be repaired
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15.
Which of the following is true about chromatin
structure in cells
– Compacted chromatin is more radiosensitive than
non-compacted chromation
– During mitosis cells decompact their chromatin
and become radiosensitive
– Compact chromatin in S phase mediates
radioresistancy
– Compaction facilitates gene transcription
#1 –compaction occurs in mitosis, which is why
chromosomes can be seen under the microscope during
this phase
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16. Which of the following is correct about
alpha-type cell killing following radiation
exposure
– It represents single lethal hits
– It is due to accumulated damage
– It requires intertrack interactions
– It is not oxygen dependent
#1 – Intratrack lesions dominate and accumulated
damage plays only a small role
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17. Which of the following radiobiological
phenomena occurring between dose
fractions has little or no effect on normal
tissue radiation responses?
– Repair
– Redistribution of cells in the cell cycle
– Repopulation
– Reoxygenation
#4 – Normal tissues are generally considered to be well
oxygenated
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