Transcript RADIOBIOLOGY

RADIOBIOLOGY
HUMAN BIOLOGY
RADIOBIOLOGY:
THE STUDY OF THE EFFECTS
OF IONIZING RADIATION ON
BIOLOGIC TISSUE
EARLY EFFECTS OF
RADIATION ON HUMANS
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HEMATOLOGIC SYNDROME
G.I. SYNDROME
CNS SYNDROME
TISSUE DAMAGE-ERYTHEMA,
DESQUAMATION
• HEMATOLOGIC DAMAGE
• CYTOGENIC DAMAGE
LATE EFFECTS
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LEUKEMIA
BONE CANCER
BREAST CANCER
THYROID CANCER
LOCAL TISUE DAMAGE
LIFESPAN SHORTENING
GENETIC DAMAGE
CYTOGENIC DAMAGE
FETAL IRRADIATION EFFECTS
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PRENATAL DEATH
NEONATAL DEATH
CONGENITAL MALFORMATION
CHILDHOOD MALIGNANCY
DIMINISHED GROWTH AND
DEVELOPMENT
RADIATION EFFECTS IN
HUMAN POPULATIONS
• AMERICAN
RADIOLOGISTS
• URANIUM MINERS
• RADIUM WATCH DIAL
PAINTERS
• PATIENTS TREATED WITH I
• PATIENTS WITH
ANKYLOSIS SPONDYLITIS
• THOROTRAST
TREATMENT PATIENTS
• CYCLOTRON WORKERS
• LEUKEMIA, LIFE SHORT.
• LUNG CANCER
• BONE CANCER
• THYROID CANCER
• LEUKEMIA
• LIVER CANCER
• 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:
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80%
25.7%
10.7%
2.4%
0.1%
O.1%
0.8%
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02
H2
C
N2
P
S
TRACE ELEMENTS
MOLECULAR COMPOSITION
OF THE BODY
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80%
15%
2%
1%
1%
1%
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WATER
PROTEIN
LIPIDS
CARBOHYDRATES
NUCLEIC ACID
OTHER
WATER –H20
MACROMOLECULES
VERY LARGE MOLECULES
CONSISTING OF MANY
ATOMS- SOMETIMES
THOUSANDS
MACROMOLECULES
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PROTEINS
LIPIDS
CARBOHYDRATES
NUCLEIC ACIDS
MITOSIS
RADIATION DAMAGE
ANALYZED DURING METAPHASE
CELL RESPONSE TO
RADIATION
• LYNPHOCYTES
• SPERMATOGONIA
RADIOSENSITIVE
• 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
α
X-RAYS
LET
LOW LET
• GAMMA RAYS
• X-RAYS
HIGH LET
• ALPHA PARTICLES
• IONS OF HEAVY
NUCLEI
• 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
OCCURS AS A RESULT
OF THE IONIZATION
OF ATOMS ON
MASTER
OR KEY MOLECULE
EFFECTS PRODUCED BY
REACTIVE FREE
RADICALS CREATED
BY THE
INTERACTIONOF
RADIATION WITH
WATER MOLECULE
DIRECT ACTION
• THE IONIZATION OR EXCITATION OF
THE ATOMS OF BIOLOGIC
MACROMOLECULES RESULTS IN
THE BREAKAGE OF
MACROMOLECULES’
CHEMICAL BONDSMACROMOLECULE BECOMES
ABNORMAL STRUCTURE
INDIRECT ACTIONRADI0LYSIS OF WATER
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HOH +
HOH + e HOH HOH +
HOH H + + OH OH * + H *
OH * + OH *
H * + O2
HO2
RADIATION
HOH + + e
H + + OH *
OH - + H *
HOH ( NO DAMAGE)
HOH ( NO DAMAGE)
H2O2
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
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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 INFOSERIOUS 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
DEPRESSION
• 25 RAD
• 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
• LEUKEMIA
• SKIN CANCER
• NONLINEAR
TRESHOLD
• LINEAR NONTRESHOLD
• TRESHOLD
RELATIONSHIP
FIRST TRIMESTER OF
PREGNANCY THE MOST
RADIOSENSITIVE PERIOD
FIRST 2 WEEKS OF
PREGNANCY
ALL-OR-NOTHING
RESPONSE
RADIATION MONITORING
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OSL
POCKET DOSIMETER
TLD
GEIGER-MULLER DETECTOR
CUTIE PIE