CELLULAR

RADIOBIOLOGY
BASILIO BAYLON BERMUNDO BUNGAY CAPISTRANO
CARRIED CO CRUZ ESTEBAN FERNANDEZ
SUBTOPICS
■ Target Theory ■ Linear Energy Transfer
– Direct and Indirect Effects – High and Low LET
– Low LET and High LET ■ Relative Biologic Effectiveness
– DNA as target molecule ■ Oxygen Enhancement Ratio
– Cell lethality – Anoxic Cells
– OER
– Hypoxic Cells
■ Cell Survival Kinetics
– Law of Poisson Distribution
– Relationship of Radiation Dose to
Cell Survival
– Recovery
– Cell Cycle Effects
DIRECT AND INDIRECT EFFECT
■ DIRECT EFFECT
– Initial Ionizing event that
occurs in the target
molecule DNA
■ INDIRECT EFFECT
– Requires a distance in order
for the initial ionizing event
to happen
– Transfer of energy
DIRECT AND INDIRECT EFFECT
■ Radiation damage to
molecules which exist in
OVERABUNDANCE inside
the cell would NOT result in
noticeable injury of the cell
■ Radiation damage to
molecule which is NOT
ABUNDANT, such as nucleic
acid (1%) could affect the
cell SEVERELY
TARGET THEORY

■ For a cell to die after radiation exposure, its target

molecule must be inactivated.
■ Could represent Cell Lethality
TARGET
■ Considered to be an AREA of the cell occupied by
the deoxyribonucleic acid (DNA)

*The interaction between radiation and cellular

composition is RANDOM
HIT

■ Term used when radiation interact with the target

or molecules
■ Both in Direct and Indirect effects

*The principal effect of radiation on human is indirect

CONSEQUENCE OF TARGET
THEORY
■ Low LET Radiation; Absence of Oxygen
– Result: LOW probability of HIT
– Rationale: Because of the relatively large distance
between Ionizing events
■ Low Let; Presence of Oxygen
– Result: INCREASED probability of HIT
– Rationale: Free Radicals Formation
CONSEQUENCE OF TARGET
THEORY
■ High LET Radiation; Absence of Oxygen
– Result: HIGH probability of HIT
– Rationale: The distance between ionization is so close
■ High Let; Presence of Oxygen
– Result: No additional HITS
CELL SURVIVAL
KINETICS
LAW OF POISSON
DISTRIBUTION
■ First drop, 1 out of 100 become wet
■ Second drop, probably fall on the dry square not on the already wet (2 out of 100 becomes wet)
■ Third drop, probably (3 out of 100 becomes wet)
■ Totally of 97 dry 3 wet squares
■ Raindrop(increases), probably the wet square would be hit 2 or more drops
■ "raindrops falling randomly" , probability of the wet that a square become wet (law of poisson
distribution)
■ Raindrop=# of squares (100 in this case) 63% becomes wet 37% dry
*note: raindrop is falling randomly, there is a probability that one square will be hit twice or more
■ If the raindrop falls equally 100 squares will be wet with 100 raindrops
■ Raindrop (200), dry square( 100) probability is 14 squares will be dry
■ Raindrop(300),dry square (100) probability is 5 squares will be dry
■ Like a raindrop radiation interacts randomly with matter
■ Raindrop(radiation), squares(matter)
 RELATIONSHIP OF RADIATION
DOSE IN CELL SURVIVAL
■ Very low Radiation Doses Cell survival is nearly 100%
■ As the Radiation Dose increases fewer cells survive
■ At high radiation dose all cells that survive has one target hit
■ As the Doses increases some cells will sustain two or more hits,
all hits per target in excess of one represent wasted

*Hit is not simply ionizing event but rather an ionization that

inactivates the target molecule
*EXTRAPOLATION NUMBER is also called target number
 TWO MODELS
OF CELL SURVIVAL
RESULT
SINGLE-TARGET, SINGLE-HIT MODEL
MULTI-TARGET,SINGLE-HIT MODEL
TERMS

■ 𝐷𝑄 - threshold dose; the capacity of the cell to

recover from sublethal damage
■ 𝐷𝑜 - mean lethal dose; dose that would be
sufficient to kill the remaining 37%
■ 𝐷37 - dose that would be sufficient to kill 100%
of the cells
SINGLE-TARGET, SINGLE-HIT
■ Applies to biologic targets e.g., enzymes, viruses and
bacteria
■ As the dose increases, some cells will sustain two or more
■ All the hits per target in excess of one represent wasted
radiation dose because the bacteria had been killed already
by the first hit
SINGLE-
TARGET,
SINGLE-HIT
Examples: 1000 bacteria
• As 1000 Bacteria are irradiated
• An increase in dose
• Number of deaths will increase
• The 𝐷37 is the dose that results
in 37% survival
SINGLE-TARGET,
SINGLE-HIT
MODEL
• Radiation Dose reaches a level
sufficient to kill 63% of the cell
• 37% Survival, called as 𝐷37
indicates a highly radiosensitive
cell
• Low 𝐷37 indicates a highly
radiosensitive cell
• High 𝐷37 reveals
radioresistance
SUMMARY

■ LOW 𝐷37 - Radiosensitive

■ HIGH 𝐷37 - Radioresistant
 MULTI-
TARGET,
SINGLE-HIT
• If each pavement square
has two equal parts, each
part must be hit for the
square to be considered
wet.
• Applies to more complicated
biologic systems such as
human cells
MULTI-
TARGET,
SINGLE-HIT
The extrapolation number is
also called target number
The type of experiment was
conducted in human cells
The observed extrapolation
number was 2
SUMMARY

■ Large 𝐷𝑂 - Radioresistant
■ Small 𝐷𝑂 - Radiosensitive
RECOVERY
SUBLETHAL DAMAGE
■ -the shoulder of the graph of multi target, single-hit model shows
that the mammalian cell, some damage must be accumulated
before the cell dies.
■ - this accumulated damage is called sublethal damage .

* the wider the shoulder, the more lethal damage that can sustained
and the higher the values of DQ.
SPLIT-DOSE
IRRADIATION
- Designed to describe
the capacity of a cell to
recover from sublethal
damage
CELL CYCLE EFFECTS
■ Cell Cycle time/ Cell generation time

– -the average time when cells replicate from one

mitosis to another

– Cells that in normal proliferation usually have cell

cycle times of 24 hours. Some specialized cells have
cell cycle that extend to hundreds of hours

– Longer cell-cycle times primarily result from

lengthening of the G1 phase
CELL CYCLE EFFECTS
■ Mitosis
– process where a single cell divides into
two identical daughter cells (cell division)
■ G1 Phase
– most variable of all phases
The cell is most sensitive during the M
phase and least sensitive during the late S
phase.
CELL CYCLE EFFECTS
SUMMARY
■ G1 PHASE
– DNA is in double-helix
– Most time variable cell cycle
■ S PHASE
– DNA replication phase
– G1 – S Phase is the next most radiosensitive phase
after M phase
– Late S Phase the most radioresistant cell cycle
■ M PHASE
– Most radiosensitive cell cycle
LET
RBE
OER
LINEAR ENERGY TRANSFER
■ VERY HIGH LET
– Cell Survival Kinetics follow the single-target, single-hit
model
– Lower chance of cell survival
■ LOW LET
– Cell Survival Kinetics follow multi-target, single-hit model
– Mean lethal dose after irradiation is greater
– Higher chance of cell survival after exposure than High
LET
LINEAR ENERGY TRANSFER

■ At very high LET follows the

single-target, single-hit model
■ At low LET radiation the multi-
target, single-hit model applies
So low LET means (?) greater than
High LET

*Low radiation doses, cell survival is

nearly 100%
*high radiation doses, fewer cells
survive that have one target hit
RELATIVE BIOLOGIC
EFFECTIVENESS (RBE)
■ Describes the ability to produce biologic damage as LET
increases
■ RBE of diagnostic x-rays is 1
– Low LET ; RBE <1
– High LET; RBE >1
SAMPLE PROBLEM
■ When mice are irradiated with 250-kVp x-rays, death
occurs at 6.5 Gyt (650 rad). If similar mice are
irradiated with fast neutrons, death occurs at only 2.1
Gyt (210 rad). What is the RBE for the fast neutrons?

6.6 𝐺𝑌𝑡
■ Answer: RBE =
2.1 𝐺𝑌𝑡
OXYGEN ENHANCEMENT
RATIO ( OER )
■ Ratio of dose necessary to produce a given effect
under anoxic(without oxygen) conditions to the
dose necessary to produce the same effect under
aerobic(with oxygen) conditions
■ OXYGEN EFFECT
– Characteristics of tissue radiation response
OXYGEN ENHANCEMENT
RATIO ( OER )
■ Oxygen presence increases radiation
effectiveness in cell killing
■ Lack of oxygen results in radioresistant
cells
■ The oxygen enhancement ratio (OER) is high
for low linear energy transfer radiation and
decreases in value as the LET increases.
SAMPLE Answer:

PROBLEM Low LET, no oxygen 𝐷𝑜 = 3.40 Gyt

Low LET, oxygen 𝐷𝑜 = 1.40 Gyt

What is the estimated OER for
human cells exposed to low-LET 3.40 𝐺𝑦𝑡
𝑂𝐸𝑅 = = 2.4
radiation and to high-LET 1.40 𝐺𝑦𝑡
radiation?

High LET, no oxygen 𝐷𝑜 = 0.90 Gyt

High LET, oxygen 𝐷𝑜 = 0.70 Gyt

0.90 𝐺𝑦𝑡
𝑂𝐸𝑅 = = 1.3
0.70 𝐺𝑦𝑡
REFERENCE

■ Radiologic Science for Technologist, Physics, Biology and

Protection, 10th Edition, Stewart C. Bushong, pp. 494-502