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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 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 RADIATION EFFECT CELL THEORYTHEORY
• 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 ATOMIC COMPOSITION OF BODY:BODY:
• 80%• 25.7%• 10.7%• 2.4%• 0.1%• O.1%• 0.8%
• 02
• H2
• C
• N2
• P• S• TRACE ELEMENTS
MOLECULAR COMPOSITION OF THE BODY
• 80%• 15%• 2%• 1%• 1%• 1%
• WATER• PROTEIN• LIPIDS• CARBOHYDRATES• NUCLEIC ACID• OTHER
WATER –HWATER –H2200
MACROMOLECULESMACROMOLECULES
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• SPERMATOGONIA
• OSTEOBLASTS• SPERMATIDS• MUSCLE CELL
• NERVE CELL
RADIOSENSITIVE
RADIORESISTANT
Radiation Biology
LAW OF BERGOINE AND TRIBONDEAU
Have a long mitotic future
1906 Bergonie and Tribondeau realized that cells were most sensitive to radiation when they are:
Rapidly dividing
Undifferentiated
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
LETLET
• GAMMA RAYS
• X-RAYS
• ALPHA PARTICLES• IONS OF HEAVY
NUCLEI• CHARGED
PARTICLES• LOW ENERGY
NEUTRONS
LOW LET HIGH LET
LOW LET RADIATION DAMAGE TO BIOLOGIC
TISSUE:
INDIRECT ACTIONINDIRECT ACTION
HIGHT LET RADIATION DAMAGE TO BIOLOGIC
TISSUE:
DIRECT ACTIONDIRECT 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, BIOLOGIC DAMAGE OCCURS AS A RESULT OF THE IONIZATION OF ATOMS ON MASTER
OR KEY MOLECULE
• INDIRECT ACTIONEFFECTS 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 BONDS- MACROMOLECULE BECOMES ABNORMAL STRUCTURE
INDIRECT ACTION- RADI0LYSIS OF WATER
• HOH + RADIATIONRADIATION 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 DAMAGELOSS 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 MUTATION
SINGLE STRAND BRAKESRELATIVELY
INCONSEQUENTIAL IN TERMS OF CELL KILLING. WILL BE
EFFICIENTLY REPAIRED , WITH LITTLE, IF ANY,
LONG TERM CONSEQUENCES TO
THE CELL
DOUBLE STRAND BRAKESVERY 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
• LATENT
• HAMATOLOGIC
• GI
• CNS
• > 100 RAD
• 100-10,000 RAD
• 200-1,000 RAD
• 1,000-5,000 RAD
• 5,000 RAD
EARLY EFFECTS TRESHOLD DOSES
• DEATH (WB)
• HEMATOLOGIC DEPRESSION
• SKIN ERYTHEMA
• EPILATION
• GONADAL DYSFUNCTION
• 200 RAD
• 25 RAD
• 200 RAD (600 RAD)
• 300 RAD (700 RAD)
• 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 NON-TRESHOLD
• 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