RADIOSENSITIVITY

AND
RESPONSE
BEA ANTONETTE E. DOMINGO, RRT
 RADIOSENSITIVITY

Refers to the response of biological

tissues to radiation
 In 1906, two freshmen: Jean Bergonie
and Louis Tribondeau, performed an
extensive experiments on RODENT
TESTICLES
 A. Law of Bergonie and Tribondeau

 States that “radiosensitivity of cells is DIRECTLY PROPORTIONAL

to their reproductive activity and INVERSELY PROPORTIONAL to
their degree of differentiation”

 This means that radiosensitivity increases with:

1. Increased rate of cell division
2. Low degree of specialization (stem cells are very radiosensitive)
3. Higher metabolic rate
4. Increased oxygenation
5. Increased length of time they are actively proliferating
 Differentiated vs Undifferentiated Cells
 DIFFENTIATION
- Refers to the sum processes whereby undifferentiated cells
become specialized functionally and/or morphologically

1. DIFFERENTIATED CELLS 2. UNDIFFERENTIATED CELLS

- Specialized functionally - It is an immature cell whose
and/or morphologically. primary function is to divide,
- It can be considered a thus providing cells a way to
MATURE CELL OR END maintain its population and to
CELL in a population. replace mature cells lost from
- -cyte the end population
- -blast / gonia
 MITOTIC RATE

○ A measure of how fast cancer cells are

dividing and growing.
○ An increased in rate of cell division, the
higher the radiosensitivity
  METABOLIC RATE

- How quickly fuels (such as sugars) are broken down to keep the
organism's cells running.

 How does metabolism relate to cells?

- Cell metabolism is a network of biochemical reactions transforming metabolites to fulfill biological

functions. At the core of this biochemical network there are catabolic pathways that break down
molecules to generate energy, which is then used to fuel biosynthetic processes and to do
mechanical work.

- Small cells are metabolically more active than bigger cells because of more surface area to volume
ratio of smaller cells. Small cells have more surface area compared to volume, thus rate of diffusion
of nutrients and wastes across the cell membrane is faster.
CELL SURVIVAL AND
RECOVERY
 FACTORS THAT AFFECT RADIOSENSITIVITY

PHYSICAL FACTOR BIOLOGICAL FACTOR

1. LET 1. OXYGEN EFFECT

2. RBE CHEMICAL FACTOR

3. FRACTIONATION 1. RADIOPROTECTANTS

4. PROTRACTION 2. RADIOSENSITIZERS
PHYSICAL
FACTOR
RELATIONSHIP OF LET AND RBE

 LET (LINEAR ENERGY TRANSFER)

-The rate at which energy is absorb in the body.

 RBE (RELATIVE BIOLOGIC EFFECTIVENESS)

-How effective ionization radiation have caused.

“AS LET INCREASES THE RBE ALSO

INCREASES”
 FRACTIONATION VS PROTRACTION

● FRACTIONATION ● PROTRACTION
○ the process of dividing a dose ○ Dose is delivered continuously
of radiation into multiple but a lower dose rate
“fractions”

○ The dose is delivered at the

same dose in equal portions at
regular interval
IMPORTANCE OF THE TWO

● INTRACELLULAR REPAIR

○ This practices seek to maximize the destruction of malignant cells while minimizing
damage to healthy tissues.

○ The capability of the cell to repair sub-lethal damage thus recovering from radiation
injury

○ When the same amount of dose is given in fractions, the number of cells surviving
increased with time between fractions

○ The two causes less effect because time is allowed for intracellular repair and tissue
recovery
BIOLOGICAL
FACTOR
OXYGEN EFFECT (OER)

○ HOW THE PRESENCE OF OXYGEN IN IONIZING

RADIATION CAN BE DAMAGINGTO THE TISSUES

○ This could be for repair or to kill unwanted cell.

CHEMICAL
FACTOR
RADIOPROTECTANTS

○ COMPOUND THAT ACTS BY REDUCING THE

EFFECTIVE DOSE OF RADIATION TO THE CELLS

○ THEY ARE KNOWN AS THE MODIFYING

COMPOUNDS

○ CHEMICALS THAT CONTAIN GROUP OF SULFUR

AND HYDROGEN BOUND TOGETHER.

○ CYSTEINE AND CYSTEAMINE

RADIOSENSITIZER

○ INCREASES THE CELL KILLING EFFECT OF

A GIVEN DOSE OF RADIATION

○ OXYGEN – MOST POWEFUL

RADIOSENSITIZER

- ENHANCE THE RESPONSE OF AN

ORGANISM TO RADIATION
 RECOVERY / REPAIR

○ CAN OCCUR WHEN CELLS ARE EXPOSED

TO SUBLETHAL DOSES OF IONIZING
RADIATION

○ IN THE REPAIR OF SUBLETHAL DAMAGE,

OXYGENATED CELLS HAVE BETTER
PROSPECT FOR RECOVERY THAN HYPOXIC
(POORLY OXYGENATED) CELLS.
 SYSTEMATIC
RESPONSE TO
RADIATION
 TISSUE AND ORGAN IRRADIATION

○ The sensitivity of a tissue / organ to radiation

is a function of the most sensitive cell in that
particular tissue or organ
○ Organs that contain radiosensitive cells will be sensitive to radiation

○ Organs that contain radioresistant cells will be resistant to radiation

 TYPES OF
RADIATION EFFECT
 EMBRYOLOGIC
RADIATION EFFECTS IN UTERA

GENETIC
RADIATION EFFECTS ON FUTURE GENERATION

SOMATIC
-RADIATION EFFECTS APPEARING ON THE EXPOSED PERSON
(SYSTEMATIC AND TOTAL BODY RESPONSE)
TYPE ACCORDING TO TIME OF OCCURRENCE

● LENGTH OF TIME FROM THE MOMENT OF IRRADIATION TO THE FIRST

APPEARANCE OF SYMPTOMS OF RADIATION DAMAGE

LATE EARLY
- MINUTES
- DAYS - MONTHS
- HOURS - YEARS
- WEEKS
TYPE ACCORDING TO PROBABILITY

STOCHASTIC
- RADIATION EFFECTS THAT OCCUR BY CHANCE
- ALSO CALLED STATISTICAL RESPONSE (PROBABILITY OF OCCURRENCE
OF EFFECT INCREASES IN PROPORTION TO RADIATION DOSE)

DETERMINISTIC
- RADIATION EFFECTS THAT INCREASES THE SEVERITY OF RESPONSE WITH
DOSE AND A THRESHOLD IS ASSUMED.
- ALSO CALLED CERTAINTY EFFECT BECAUSE AT HIGH DOSES, CERTAIN
EFFECTS WILL OCCUR.
DOSE RESPONSE
RELATIONSHIP
 -ATTEMPT TO PREDICT THE RISK OF
OCCURRENCE OF MALIGNANCIES IN HUMAN
POPULATIONS THAT HAVE BEEN EXPOSED TO
LOW LEVEL OF IONIZING RADIATION

- DEMONSTRATED GRAPHICALLY THROUGH A

CURVE THAT MAPS THE OBSERVED EFFECTS
OF RADIATION EXPOSURE IN RELATION TO THE
DOSE OF RADIATION RECEIVED.
 LINEAR RELATIONSHIP

LINEAR NON-LINEAR
- CURVED TO SOME DEGREE
- REPRESENT BY A STRAIGHT LINE - INDICATES THAT THE BIOLOGIC
- INDICATES THAT THE BIOLOGIC EFFECTS OBSERVED INCREASES IN
EFFECTS OBSERVED INCREASES IN PROPORTION WITH DOSE BUT
PROPORTION WITH RADIATION DOSE DECREASES AS SOME POINT
 THRESHOLD RELATIONSHIP

NON-THRESHOLD THRESHOLD
- A POINT AT WHICH A RESPONSE OR
- INDICATES THAT ANY RADIATION
REACTION TO AN INCREASING
DOSE HAS THE CAPABILITY TO
STIMULATION FIRST OCCURS
PRODUCE BIOLOGIC EFFECTS
 LINEAR THRESHOLD

LINEAR NON- THRESHOLD

NON-LINEAR NON- THRESHOLD

NON-LINEAR THRESHOLD
 RECALL!!!

GENETIC EFFECTS
EMBRYOLOGIC EFFECTS
GENETIC EFFECT
 EFFECT THAT AFFECTS THE FUTURE GENERATION DUE TO
MUTATION OF DNA

EMBRYOLOGIC EFFECT
 IRRADIATION OF THE UTERO
 THERE ARE THREE GENERAL EFFECTS:

1. LETHALITY
2. CONGENITAL ABNORMALITY
3. LATE EFFECTS
STAGES OF GESTATION

-THE TYPE OF DAMAGE TO EMBRYO IS

DEPENDENT ON THE TIME OF GESTATION

- THREE STAGES:
1. PRE IMPLANTATION
2. MAJOR ORGANOGENESIS
3. FETAL STAGE
PRE IMPLANTATION

- 0-9 DAYS AFTER CONCEPTION

- 10 R DEATH OCCURS
ORGANOGENESIS

- 10 DAYS TO 12 WEEKS AFTER CONCEPTION

- 25 R = SPECIFIC ABNORMALITIES OCCURS

 FETAL STAGE

- 12 WEEKS TO TERM AFTER CONCEPTION

- IRRADIATION IN THIS STAGE RESULTED TO

FEWER ABNORMALITIES AND DECREASED
INCIDENCE OF DEATH BUT LATE EFFECTS
MAY OCCUR
 SOMATIC
IRRADIATION
LETS RECALL
 EARLY DETERMINISTIC SOMATIC EFFECTS

 STAGES OF ARS

1. PRODROMAL

2. LATENT

3. MANIFEST
a. HEMATOPOIETIC

b. GIS

c. CEREBROVASCULAR

4. RECOVERY/DEATH
LATE DETERMINISTIC
SOMATIC EFFECT
DIRECTLY RELATED TO THE DOSE RECEIVED AND THE
DEVELOPING CHANGES OF THE BODY CAUSED BY
RADIATION EXPOSURE HAPPENS AT A SLOW PACE
 INTEGUMENTARY
 EARLY EFFECTS: INFLAMMATION, ERYTHEMA, DRY AND MOIST
DESQUAMATION
 LATE EFFECTS: ATROPHY, FIBROSIS, DECREASED OR INCREASED
PIGMENTATION, ULCERATION, NECROSIS, AND CANCER
 OTHER EFFECTS: EPILATION / ALOPECIA FOR HAIR FOLLICLE
GLANDULAR ATROPHY AND FIBROSIS FOR
SWEATGLANDS

THRESHOLD: 600 RADS

 HEMATOPOIETIC
 DECREASE IN NUMBER OF STEM CELLS IN THE BONE MARROW

THRESHOLD: 25 RADS
 DIGESTIVE
 STOMACH: ULCERATION, ATROPHY, FIBROSIS
 MOUTH AND ESOPHAGUS: MUCOSITIS AND ESOPHAGITIS, ESOPHAGEAL
STRICTURE
 SMALL INTESTINE: SHORTENING OF MICROVILLI

THRESHOLD: 1000-2000 RADS

 LIVER
 RADIATION HEPATITIS CHARACTERIZED BY CIRRHOSIS, NECROSIS,
JAUNDICE AND LIVER FAILURE

THRESHOLD: 3500-4500 RADS

 REPRODUCTIVE
 TEMPORARY AND PERMANENT STERILITY AND CHROMOSOMAL
DAMAGE

THRESHOLD (TEMPORARY): 200 RADS

THRESHOLD (PERMANENT) MALE : 500-600 RADS
FEMALE: 625 RADS
CARDIOVASCULAR
 HEART: PERICARDITIS AND PANCARDITIS
 PETECHIAL HEMORRHAGE, TELEANGIECTASIA, VESSEL SCLEROSIS

THRESHOLD: 4000 RADS

 RESPIRATORY
 RADIATION PNEUMONITIS

THRESHOLD: 2500 RADS

 SKELETAL
 ALTERATION IN SIZE AND SHAPE OF BONE
 SCOLIOSIS

THRESHOLD: 2000 RADS

 URINARY
 RADIATION NEPHRITIS
 EDEMA OF KIDNEY

THRESHOLD: 2600 RADS

 CNS
 MYELITIS
 FIBROSIS OF BRAIN AND SPINAL CORD
 NECROSIS

THRESHOLD: 5000 RADS

 EYES
 CATARACTOGENESIS

THRESHOLD: 400 RADS

LATE STOCHASTIC
SOMATIC EFFECT
LATE RESPONSES IN THE BODY TO RADIATION EXPOSURE
THAT DO NOT HAVE THRESHOLD, OCCUR IN ARBITRARY
MANNER AND HAVE A SEVERITY THAT DOES NOT DEPEND
ON THE DOSE
 CARCINOGENESIS
 EXPOSURE TO IONIZING RADIATION MAY CAUSE CANCER AS A LATE
STOCHASTIC EFFECT
 AT HIGH DOSES, THE RISK IS MEASURABLE IN HUMAN POPULATION
 AT LOW DOSES (BELOW 0.1 Sv) RISK IS NOT DIRECTLY MEASURABLE IN
POPULATION STUDIES BECAUSE IT IS OVERSHADOWED BY OTHER
CAUSES.
 LIFE SPAN
SHORTENING
 PRIMARY EFFECT OF ACUTE TOTAL BODY EXPOSURE WHICH IS
DEPENDENT ON THE DOSE
 MODERATE TO HIGH DOSES OF TOTAL BODY IRRADIATION ARE
CONSIDERABLY LETHAL.
 LD 50/60
 LETHAL DOSE NECESSARY TO KILL 50% OF THE POPULATION IN 30
DAYS
RISK ESTIMATES
THIS IS TO PREDICT CANCER INCIDENCE MAY BE GIVEN IN
TERMS OF ABSOLUTE OR RELATIVE RISKS CAUSED BY
SPECIFIC EXPOSURE TO IONIZING RADIATION
3 TYPES OF RISK ESTIMATES

1. RELATIVE RISK
2. ABSOLUTE RISK
3. EXCESS RISK
 RELATIVE RISK
 IN PERCENTAGES THAN A SPECIFIC NUMBER OF CASES

 PREDICTS THAT THE NUMBER OF EXCESS CANCERS WILL INCREASE

AS A NATURAL INCIDENCE OF CANCER INCREASES WITH ADVANCING
AGE IN POPULATION

 THE CONCEPT OF RR IS USED WHEN SOMEONE OBSERVES A LARGE

POPULATION FOR STOCAHSTIC RADIATION EFFECTS WITHOUT HAVING
ANY PRECISE KNOWLEDGE OF THE RADIATION DOSE TO WHICH THEY
WERE EXPOSED.

 RELATIVE RISK = OBSERVED CASES / EXPECTED CASES

ABSOLUTE RISK
 If atleast two different dose levels are known,
then it may be possible to determine an
absolute risk factor.
 AR consists of units of cases/population/dose
 Predicts that a specific number of excess
cancers will occur as a result of exposure.
 EXCESS RISK
 When an investigation of human radiation response
reveals the induction of some stochastic effect, the
magnitude of the effect is reflected by the excess
number of cases induced.
 If a specific CA incidence in an irradiated population
exceeds that which is expected, then the difference
between the observed number of cases ad the
expected number would be the EK.
 ER = OBSERVED CASES – EXPECTED CASES
 THANK YOU
SO MUCH
FUTURE RRTs
BEA ANTONETTE ENCISO DOMINGO