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RADIOBIOLOGY

HUMAN BIOLOGY
RADIOBIOLOGY:

THE STUDY OF THE EFFECTS


OF IONIZING RADIATION ON
BIOLOGIC TISSUE
EARLY EFFECTS OF
RADIATION ON HUMANS
• HEMATOLOGIC SYNDROME
• G.I. SYNDROME
• CNS SYNDROME
• TISSUE DAMAGE-ERYTHEMA,
DESQUAMATION
• HEMATOLOGIC DAMAGE
• CYTOGENIC DAMAGE
LATE EFFECTS
• LEUKEMIA
• BONE CANCER
• BREAST CANCER
• THYROID CANCER
• LOCAL TISUE DAMAGE
• LIFESPAN SHORTENING
• GENETIC DAMAGE
• CYTOGENIC DAMAGE
FETAL IRRADIATION EFFECTS

• PRENATAL DEATH
• NEONATAL DEATH
• CONGENITAL MALFORMATION
• CHILDHOOD MALIGNANCY
• DIMINISHED GROWTH AND
DEVELOPMENT
RADIATION EFFECTS IN
HUMAN POPULATIONS
• AMERICAN • LEUKEMIA, LIFE SHORT.
RADIOLOGISTS • LUNG CANCER
• URANIUM MINERS
• BONE CANCER
• RADIUM WATCH DIAL
PAINTERS
• PATIENTS TREATED WITH • THYROID CANCER
I
• PATIENTS WITH • LEUKEMIA
ANKYLOSIS SPONDYLITIS
• THOROTRAST
TREATMENT PATIENTS • LIVER CANCER

• CYCLOTRON WORKERS • CATARACTS


RADIATION EFFECT CELL
THEORY
• RADIATION INTERACTION AT THE
ATOMIC LEVEL CAN PRODUCE
MOLECULAR CHANGE, AS A
RESULT, CELL WILL BE PRODUCED
DEFICIENT
IN NORMAL GROWTH AND
METABOLISM
ATOMIC COMPOSITION OF
BODY:
• 80% • 02
• 25.7% • H2
• 10.7% • C
• 2.4% • N2
• 0.1% • P
• O.1% • S
• 0.8% • TRACE ELEMENTS
MOLECULAR COMPOSITION
OF THE BODY
• 80% • WATER
• 15% • PROTEIN
• 2% • LIPIDS
• 1% • CARBOHYDRATES
• 1% • NUCLEIC ACID
• 1% • OTHER
WATER –H20
MACROMOLECULES

VERY LARGE MOLECULES


CONSISTING OF MANY
ATOMS- SOMETIMES
THOUSANDS
MACROMOLECULES
• PROTEINS
• LIPIDS
• CARBOHYDRATES
• NUCLEIC ACIDS
MITOSIS
RADIATION DAMAGE

ANALYZED DURING METAPHASE


CELL RESPONSE TO
RADIATION
• LYNPHOCYTES RADIOSENSITIVE
• SPERMATOGONIA

• OSTEOBLASTS
• SPERMATIDS
• MUSCLE CELL

• NERVE CELL RADIORESISTANT


Radiation Biology
LAW OF BERGOINE AND
TRIBONDEAU
1906 Bergonie and Tribondeau
realized that cells were most
sensitive to radiation when
they are:

    Rapidly dividing

    Undifferentiated

 
Have
 
a long mitotic future
RADIATION ENERGY
TRANSFER DETERMINANTS
• LET
• RBE
• OER
LET-LINEAR ENERGY
TRANSFER
• THE AVERAGE ENERGY DEPOSITED
PER UNIT LENGTH OF TRACK

keV/ μm
LET

X-RAYS
LET
LOW LET HIGH LET

• GAMMA RAYS • ALPHA PARTICLES


• IONS OF HEAVY
NUCLEI
• X-RAYS
• CHARGED
PARTICLES
• LOW ENERGY
NEUTRONS
LOW LET RADIATION
DAMAGE TO BIOLOGIC
TISSUE:

INDIRECT ACTION
HIGHT LET RADIATION
DAMAGE TO BIOLOGIC
TISSUE:

DIRECT ACTION
DIRECT & INDIRECT
ACTION
INDIRECT ACTION
RBE –RELATIVE BIOLOGIC
EFFECTIVENESS

• RELATIVE CAPABILITIES OF OF
RADIATION WITH DIFFERING LETs
TO PRODUCE PARTICULAR
BIOLOGIC RESPONSE
RBE

DOSE IN Gy FROM 250 KVP X-RAYS

DOSE IN GRAY OF TEST RADIATION


LET RBE
RBE QF (QUALITY FACTOR)
OER-OXYGEN ENHANCEMENT
RATIO
• THE RATIO OF THE RADIATION DOSE
REQUIRED TO CAUSE A
PARTICULAR BIOLOGIC RESPONSE
OF CELLS OR ORGANISMS IN AN
OXYGEN DEPRIVED ENVIRONMENT
TO THE RADIATION DOSE REQUIRED
TO CAUSE AN IDENTICAL RESPONSE
UNDER NORMAL OXYGENATED
CONDITIONS
LET OER
DOSE FRACTIONATION
&
PROTRACTION

LOWER THE EFFECT OF


THE RADIATION DOSE
HORMESIS?
RADIATION
DOSE
RESPONSE
CANCER, LEUKEMIA,
&
GENETIC EFFECTS
FOLLOW:

LINEAR NON-TRESHOLD DOSE RESPONSE


RELATIONSHIP
SKIN EFFECTS DURING
FLUORO FOLLOW:

SIGMOID DOSE RESPONSE


RELATIONSHIP
DIRECT & INDIRECT
ACTION
• DIRECT ACTION, • INDIRECT ACTION
BIOLOGIC DAMAGE EFFECTS PRODUCED BY
OCCURS AS A RESULT REACTIVE FREE
OF THE IONIZATION RADICALS CREATED
OF ATOMS ON BY THE
MASTER INTERACTIONOF
OR KEY MOLECULE RADIATION WITH
WATER MOLECULE
DIRECT ACTION
• THE IONIZATION OR EXCITATION
OF THE ATOMS OF BIOLOGIC
MACROMOLECULES RESULTS IN
THE BREAKAGE OF
MACROMOLECULES’
CHEMICAL BONDS-
MACROMOLECULE BECOMES
ABNORMAL STRUCTURE
INDIRECT ACTION-
RADI0LYSIS OF WATER
• HOH + RADIATION HOH + + e
• HOH + e HOH -
• HOH + H + + OH *
• HOH - OH - + H *
• H + + OH - HOH ( NO DAMAGE)
• OH * + H * HOH ( NO DAMAGE)
• OH * + OH * H2O2
• H * + O2 HO2
X-RAY PHOTON

FAST ELECTRON

ION RADICAL

FREE RADICAL

CHEMICAL CHANGE

BIOLOGIC EFFECT
MOST DAMAGE COMES
FROM OH * RADICAL
INDIRECT ACTION ON
MACROMOLECULE
EFFECTS OF IONIZING
RADIATION ON DNA

• BASE DAMAGE
• SINGLE STRAND BRAKE
• DOUBLE STRAND BRAKE
• CROSSLINKING
BASE DAMAGE
LOSS OR CHANGE OF A
BASE ON DNA RESULTS
IN ALTERATION OF THE
BASE SEQUENCE.
SEQUENCE OF THE BASE
STORES GENETIC INFO-
SERIOUS CONSEQUENCE
TO THE CELL

CLASSIFIED AS:

MUTATION
SINGLE STRAND BRAKES
RELATIVELY
INCONSEQUENTIAL
IN TERMS OF CELL
KILLING. WILL BE
EFFICIENTLY
REPAIRED , WITH
LITTLE, IF ANY,
LONG TERM
CONSEQUENCES TO
THE CELL
DOUBLE STRAND BRAKES
VERY DIFFICULT FOR
THE CELL TO BE
REPAIRED. CAN LEAD
TO CELL KILLING. IF
REPAIR DOESN’T TAKE
PLACE, THE DNA
CHAINS CAN SEPARATE.
SERIOUS
CONSEQUENCE TO CELL
LIFE.
DOUBLE STRAND BRAKES
CROSSLINKING
EARLY EFFECTS
• PRODROMAL • > 100 RAD

• LATENT • 100-10,000 RAD

• HAMATOLOGIC • 200-1,000 RAD

• GI • 1,000-5,000 RAD

• CNS • 5,000 RAD


EARLY EFFECTS TRESHOLD
DOSES
• DEATH (WB) • 200 RAD

• HEMATOLOGIC
• 25 RAD
DEPRESSION

• SKIN ERYTHEMA • 200 RAD (600 RAD)

• EPILATION • 300 RAD (700 RAD)

• GONADAL
DYSFUNCTION
• 10 RAD
LYMPHOCYTES AND
SPERMATOGONIA

MOST SENSITIVE
LD50/60
• DOSE OF RADIATION TO
THE WHOLE BODY THAT
WILL 50% OF IRRADIATED
OBJECTS TO DIE WITHIN
60 DAYS.
LD50/30
• DOSE OF RADIATION TO
THE WHOLE BODY THAT
WILL 50% OF IRRADIATED
OBJECTS TO DIE WITHIN
30 DAYS.
LATE EFFECTS RESPONSE
• CATARACT • NONLINEAR
TRESHOLD
• LEUKEMIA • LINEAR NON-
TRESHOLD

• SKIN CANCER • TRESHOLD


RELATIONSHIP
FIRST TRIMESTER OF
PREGNANCY THE MOST
RADIOSENSITIVE PERIOD
FIRST 2 WEEKS OF
PREGNANCY

ALL-OR-NOTHING
RESPONSE
RADIATION MONITORING
• OSL
• POCKET DOSIMETER
• TLD
• GEIGER-MULLER DETECTOR
• CUTIE PIE

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