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