Radiobiology Basics and Radiation principle

Radiobiology

1. Radiobiology Basics
นพ. เฉลิมภักดิ์ ศุภคติธรรม
[email protected]

2. เนื้อหาโดยสังเขป
• Introduction
• Physical and chemical effect of radiation
• Cell survival curve
• Radioprotectors and radiosensitizers
• Effect of radiation on molecules and cells

3. Sea of radiation we live in
• Scientists have studied radiation for over 100 years
• Radiation has always been around us as a part of nature.

Cosmic radiation (from outer space) at sea level (26 mrem: millirem)

The annual average dose per person from all natural and man-made
sources is about 620 mrems.
• The U.S. Nuclear Regulatory Commission (NRC) standards

up to 5,000 mrem per year (Work with and around radioactive material)
•*The reduction in life expectancy from a dose of 1 mrem is
about 1.2 minutes.

1 mrem equivalent to the reduction in life expectancy from crossing the
street three times, taking three puffs on a cigarette, or consuming 10
extra calories (for a person who is overweight).
Terrestrial Radiation: different concent rations of uranium and thorium in soil.
Internal Radiation: radioactive material inside their bodies (may be from soils)

4. รังสีDefinition
•Radiation is an energy in the form of
electro-magnetic waves or particulate
matter, traveling in the air.
•A type of radiation that is able to
disrupt atoms and molecules on which
they pass through, giving rise to ions
and free radicals.
รังสีก่อประจุIonizing Radiation
รังสีไม่ก่อประจุ : ช่วงตํ ่าของแถบ EM waves

5. ELECTROMAGNETIC RADIATIONS
Photon E = h(energy = Planck’s const x frequency)
= hc/(c = speed of light, = wave length)
10
-9
10
-8
10
-7
10
-6
10
-5
10
-4
10
-3
10
-2
10
-1
11010
2
10
3
10
4
rays
X-rays U.V.
v
i
s
i
b
l
e
InfraRed Radio Waves
Microwaves Short Waves
T.V.
Radio
Radar
IONIZING
RADIATION
NON-IONIZING RADIATION
(cms)
E (eV) 1.24x10
7
1.24x10
2
1.24x10
-13

6. กัมมันตภาพรังสี Radioactivity
•If a nucleus is unstable for any reason, it
will emit and absorb particles. There are
many types of radiation and they are all
pertinent to everyday life and health as
well as nuclear physical applications. •การแผ่รังสีได้เองอย่างต่อเนื ่องของธาตุกัมมันตรังสี
Radiobiology
•Basic principles of physics and biology:
action of ionizing radiation on biological
tissues and living organisms

7. Types of Radiation
Inspired by various images by IAEA. UNSCEAR, etc.
X-ray or
รังสีแอลฟา อันตรายถ้าสูดดม กิน หรือเข้าทางแผลเปิด:
Positively charged, helium nucleus

8. Man-Made Radiation
• Diagnostic radiology (X-rays) : The largest source of man-
made radiation
• Nuclear medicine (Radiopharmaceuticals)
• Radiotherapy (Co-60)

9. วัดปริมาณ
•รังสีที ่แผ่ออกมา

หน่วยเดิม คูรี (Ci)

หน่วยสากลเบคเคอเรล (Bq)

1 Ci = 37000 ล้าน Bq
•รังสีที ่คนได้รับหรือที ่ดูดซับโดยเนื้อเยื ่อ

หน่วยเดิม แรด (Rad = Roentgen
absorbed dose)

หน่วยสากลเกรย์(Gy = Gray)

100 Rad= 1 Gy
•รังสีสมมูล (ความเสี ่ยงสุขภาพ
จากรังสี)

หน่วยเดิม (rem =
Roentgen equivalent in
man)

หน่วยสากล ซีเวิร์ต
(Sv: Sievert)

100 rem = 1 Sv

10. Effects of ionizing radiation
onatom
Ionization Excitation
Also kinetic energy of non-ionizing radiation
to raise the thermal energy of an outer shell
electron (Excitation with emission)

11. Direct action
of ionizing radiation
Ionizing radiation + RH R
-
+ H
+
OH
I
R –C = NH
imidol (enol)
O
II
R –C = NH
2
amide (ketol)


Tautomeric shifts
Bond breaks

12. e
-
Xray
ray
P
+
O
H
H
OH
-
H
+
H
o
OH
o
Indirect action
of ionizing radiation
(free radicals or
highly reactive
species)
(ionization)
Radiolysis
Short life of free radicals (10
-10
sec), only those formed in water column
of 2-3 nm around DNA Indirect action can be modified by chemical
sensitizers or
radiation protectors

13. NORMAL IRRADIATED
Mitotic death

14. รางวัลโนเบลสาขาสรีรวิทยาหรือการแพทย์ (พ.ศ. 2489)
The Nobel Prize in Physiology or Medicine 1946
• "for the discovery of the production of mutations
by means of X-ray irradiation.“

Carcinogenic effects of X-rays

Using hereditary characteristics fruit flies
• Use for benign conditions has been limited since
•The Nobel Prize in Physiology or Medicine 1946. 
NobelPrize.org. Nobel Prize Outreach AB 2021. Wed. 
22 Jul 2021. 
<https://www.nobelprize.org/prizes/medicine/1946/
summary/>

15. DNA restoration failure
UnrejoinedDNA
double strand breaks
Incorrect repair
ofDNA damage
Cytotoxic effect
Mutations

16. Classification of radiations
•Linear energy transfer (LET) is used for defining the quality of
an ionizing radiation beam.

Linear rate of energy absorption by the absorbing
medium as the charged particle traverses the
medium.

dE/dl (dE= the average
energy locally imparted to
the medium
/ dl = in traversing a distance of dl)

keV/m
• In contrast to the stopping power (Focus energy loss by a
charged particle moving through a medium)

MeV/cm
RadiationLET keV/m
1 MeV -rays
100 kV
p
X-rays
20 keV -particles
5 MeV neutrons
5 MeV particles
0.5
6
10
20
50

17. Relation between linear energy
transfer (LET) and typeof action
Directactionispredominantcauseof
damagewithhighLETradiation,e.g.
alphaparticlesandneutrons
Indirect action is predominant (About
2/3) with low LET radiation, e.g. X
andgammarays

18. The stage of action
of ionizing radiation
Physical stage The transfer of kinetic energy from ionizing
radiation to atoms or molecules leads to
excitation and ionization of these atoms or
molecules
10
–18
–
10
–15
seconds
Physic-chemical
stage
The displace of absorbed energy of ionizing
radiation into molecules and between them.
Formation of free radicals
10
–14
–
10
–11
seconds
Chemical stage Reactions between free radicals, reactions
between free radicals and intact molecules.
Formation of molecules with abnormal
structure and function
10
–6
–
10
–3
seconds
Biological stage Formation of injures on all levels – from
cellular structures to organism and
population.
Development of processes of biological
damage and reparative processes
Seconds
– years

19. Cell survival curves
•Several factors may contribute to less
radio-sensitive cells:

Removal of oxygen to create a hypoxic
state (Especially in low level LET)

Adds a chemical radioprotectorsfor free
radical scavengers

Use of low dose rates or multi-fractionated
irradiation

Synchronization of cells in the late S phase
of the cell cycle

20. Relative Biological Effectiveness
(RBE)
Dose of standard radiation required to produce an effect
Dose of test radiation required to produce the same effect
=
S.F.
1.0
0.1
0.01
0.001
DOSE Gy
High LET
Low LET
Physical Dose = Biological Dose
S.F. = surviving fraction
Standard = historically 250 kVpx-rays
Now use: cobalt-60 gamma rays

21. Linear Energy Transfer (LET keV/m)
RELATIVE
BIOLOGICAL
EFFECTIVENESS
(for cell kill)
1000 100 10 1
0
2
4
6
8
RBE
Diagnostic
X-rays
Fast
Neutrons
Alpha
Particles overkill
0.1
Co-60
gamma rays
0
1
2
3
4
OER
OER
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
RBE and
oxygen enhancement ratio

22. RADIOPROTECTORS AND
RADIOSENSITIZERS
•Some chemical agents may alter the cell response to
ionizing radiation, either reducing or enhancing:

Radioprotectors:reduce indirect effects of radiation by
scavenging the production of free radicals.

Radiosensitizers: promote both the direct and indirect
effects of radiation

23. Tissues and living organisms
• All living entities made up of protoplasm

Inorganic and organic compounds in water
• The smallest unit of protoplasm independently exists

The cell => cytoplasm, nucleus

Somatic cells or germ cells (sperm or egg)

Mitosis or meiosis (Half of the Chromosome)
• Groups of cells => tissue
• Groups of tissues => organ
• Groups of organs => organ system = organism

24. Effect of irradiation on cells
• First, standard physical effects between
radiation and the atoms or molecules of the
cells
• Then possible biological damage to cell
functions
• Mainly effects when damage to the DNA

other sites damage may also lead to cell death
• Surviving cell (Maintains reproductive integrity and
proliferates into a large number of progeny)

25. Somatic cells
• Stem cells

Self-perpetuate and produce cells for a
differentiated cell population

2 Gyrequired to typically destroy cell function
• Transit cells

In movement to another population
• Mature cells

Fully differentiated and usually no mitotic activity

100 Gyrequired to destroy cell function

26. Possible outcomes
No effect
Permeability changes: may increase or decrease permeability
Interference of function: e.g. decreased motility
Division delay: The cell is delayed in going through division
Apoptosis: The cell programmed to die
Reproductive failure: The cell dies when attempting the mitosis
Genomic instability: Delay in cell growth and division, shorten
 life
Mutation: The cell survives but contains a mutation
Transformation: The mutation => transformed phenotype and 
possibly carcinogenesis (May takes years)
Bystander effects: An irradiated cell may send signals to 
neighboring unirradiated cells and induce genetic damage
Adaptive responses: The irradiated cell becomes more radio‐
resistant
Fate of irradiated cell
Radiation Oncology
Physics: A Handbook for
Teachers and Students

28. Study materials •Eric JH, GiacciaAJ. Radiobiology for the
Radiologist. Lippincott Williams & Wilkins, 2018 • SuntharalingamN, PodgorsakEB, Hendry JH.
Radiation Oncology Physics: A Handbook for
Teachers and Students. Vienna: IAEA publication,
2005.
• Kumar V, Abbas AK, Aster JC. Robbins and Cotran:
Pathologic Basis of Disease. 10
th
ed. Philadelphia:
Elsevier Saunders, 2021.

29. 1. Electromagnetic radiation is considered ionizing if
its photon energy is greater than
• 1.24 eV
• 12.4 eV
• 124 eV
• 1.24 keV
#3 –this is sufficient to break bonds in biological
molecules

30. 2. The lifetime of free radicals is roughly about
• 0.001 (10 exp-3) seconds
• 0.000001 (10 exp-6) seconds
• 0.000000001 (10 exp-9) seconds
• 0.000000000001 (10 exp-12) seconds

31. 3. What is the S.I. (Systèmeinternational d'unites)
unit of absorbed radiation dose?
• Becquerel
• Roentgen
•Sievert
•Gray

32. 4. Which of the following is not charged
particle?
• Heavy ion
• Electron
• Neutron
•Proton

33. 5. Which of the following is TRUE about Linear Energy
Transfer?
• It shows an inverse correlation with the oxygen
enhancement ratio
• It is a measure of the biological effectiveness of
ionizing radiation
• It is maximum at a relative biological effectiveness
of 150
MeV/cm
• It is measured in keV/micrometer