GRADUATE COURSE: PHYSICS 773

1
GRADUATE COURSE PHYSICS 773
BASIC CLINICAL RADIOBIOLOGY This is a
graduate level course designed to educate
students on the clinical applications of
radiation biology in cancer therapy.  The course
will be suitable for students in life sciences
interested in general aspects of DNA repair,
cancer biology and clinical radiation therapy. 
This basic course in radiation biology will also
be useful for radiation oncology residents
(PGY1-3) to prepare for the Canadian Royal
College of Physicians and Surgeons Fellowship
exams.  The course will be three hours per week
running from September to December and will
consist mainly of short seminars by the
instructor followed by student discussion.   Final
grades will be based on one final exam (60),
one oral research presentation (20), and
participation/attendance (20).   Location
Hamilton Regional Cancer Centre Time Wednesdays
130-430  
 
2
Unit One
         Interaction of radiation with matter
Types of ionizing radiations Radiation
chemistry Direct and indirect action of
radiation. (a) Photons Photoelectric absorption,
Compton scattering, Pair production (b) Charged
Particles Bethe-Block equation, LET, (c)
Neutrons, (d) protons (e) Origin of different
radiations.          Elementary Processes and
Water Chemistry Primary, Secondary, Chemical,
Biological, radical reactions, biochemistry and
radicals          The oxygen effectEffect of
02 concentration Time of action of oxygen
Mechanism of the oxygen effect Hypoxic cells in
solid tumors Reoxygenation Implications for
radiotherapy. Hypoxia and tumor
progression.          Linear energy
transferDefinition and examples. Relative
biological effectiveness RBE as a function of
LET, dose, dose-rate, tissue type, and oxygen
effect.
3
Unit Two
         DNA damageSingle and double strand
DNA breaks Mechanisms of DNA repair Genes
controlling DNA repair.          Repair of
radiation damagePotentially lethal damage
Sublethal damage in cells normal tissues and
tumors The dose-rate effect in cells tissues
and tumors.          Chromosal and chromatid
aberrations Dose response relationships Use of
the peripheral lymphocyte system as an in vivo
dosimeter.          Mammalian cell
radiosensitivitymitotic death and
apoptosis.          Cell survival curvesTarget
theory Linear-quadratic model Sample
calculations.          Quantitative normal
tissue systems skin clones jejunal epithelium
bone marrow colonies mouse skin pig skin etc.
4

• ) UNIT THREE
•          Solid tumor systemsExperimental
  models tumor regrowth measurements, tumor cure -
  TCD50, dilution assay technique, lung colony
  assay system, in vivo/in vitro system and
  spheroids.
•          Cell and tissue kineticsThe cell
  cycle Autoradiography percent labeled mitoses
  technique Variation of sensitivity through cell
  cycle Growth fraction Cell loss factor Volume
  doubling time Tpot Growth kinetics of human
  tumors.
•          Time-dose and fractionation The 4R's
  of radiobiology The basis of fractionation
  Early and late responding tissues Proliferation
  in normal tissues Accelerated repopulation
  Hyperfractionation Accelerated treatment
  Modified treatment schedules.
•          Predictive Assays for(a)
  Radiosensitivity of tumor and normal tissues (b)
  Cell kinetics (c) Tumor hypoxia.
• Remembered DoseRepair of injury in various
  tissues and organs. Retreatment policies.

5

• UNIT FOUR
• Alternative radiation modalitiesProtons
  Neutrons and Boron neutron capture therapy.
• Chemotherapeutic agents used as adjuvants with
  radiationClasses of agents Cycling and
  non-cycling cells The oxygen effect for
  chemotherapy agents Combination with radiation
  Drug resistance Second malignancies from
  chemotherapy agents.
•          Radiosensitizers and bioreductive
  drugs.Halogenated pyrimidines Nitroimidazoles
  Hypoxic cytotoxins.
• ProtectorsSulfhydryl compounds Amifostine
  Misoprostal.
• Hyperthermia Methods of heating Cellular
  response to heat Repair of thermal damage
  Thermotolerance Hyperthermia combined with
  irradiation Response of tumors and normal
  tissues to heat.
•          Normal Tissue EffectsDose - Time -
  Volume relationships. Target cells for acute and
  late reactions Pathology of acute and late
  reactions Classification of tissue
  radiosensitivity.

6

• UNIT FIVE
•          Radiophysiology of human
  tissuesEffects of irradiation of the skin bone
  and cartilage kidney lung nervous tissues
  ovary testis eye lymphoid tissue Effects of
  irradiation of the oral, pharyngolaryngeal and
  esophageal mucous membrane salivary glands
  Parenchymal versus stroma injury Latency between
  depletion of clonogenic cells and tissue injury.
•          Total body irradiationProdromal
  radiation syndrome Cerebrovascular syndrome
  Gastrointestinal syndrome Hematopoietic
  syndrome Mean lethal dose (LD50) Treatment of
  radiation accidents.
•          Radiation CarcinogenesisThe latent
  period Dose response malignancies in prenatally
  exposed children Second tumors in radiotherapy
  patients. Risk estimates in the human BEIR and
  UNSCEAR Committees Calculations based on risk
  estimates.
•          Heritable effects of radiationSingle
  gene mutations Chromosome aberrations Relative
  vs. absolute mutation risk Doubling dose
  Heritable effects in humans Risk estimates for
  heritable effects.
• Radiation effects in the developing embryo and
  fetusIntrauterine death Congenital
  abnormalities and neonatal death Growth
  retardation Microcephaly Mental retardation
  Dependence of the above effects on dose,
  dose-rate and stage in gestation Human
  experience of pregnant women exposed to
  therapeutic doses.

7

• UNIT SIX General (NOT COVERED IN DETAIL)
• CataractsBasic biology Latency Threshold
  Deterministic effect Relationship to dose High
  and low LET radiations
• Terminology Techniques of Molecular Biology
•          Endonucleases. Gel Electrophoresis
  Southern, Northern and Western Blots,
  Hybridization Vector Libraries Gene Transfer
  Polymerase Chain Reaction (PCR), Single Strand
  Conformal Polymorphism (SSCP) Methods of
  sequencing. Gene Cloning Strategies.
• Basic Cancer Biology
•          Oncogenes Tumor suppressor genes.
  Cytokines and growth factors. Signal Transduction
  Cancer Genetics. Chromosomal changes associated
  with leukemia and solid cancers. Multistep nature
  of cancer.
•          Gene Therapy Suicide Genes. Cancer
  vaccines. Radiation-inducible genes linked to a
  cytotoxic agent. Genetic manipulation, i.e.
  correcting the genetic defect.

8
773 Time Table Unit One September 12, 19 Unit
Two September 26, Oct 3 Unit Three Oct, 10, 17,
24 Unit Four Oct 24, 31, Nov 7 Unit Five Nov
14, 21, 28 Unit Six Nov 28 Review for Final
Exam Dec 5 Final Exam Dec 12
9
Radiation Oncology 100 Years of Therapy and
Research
10




11
(No Transcript)
12
(No Transcript)
13
History of Radiation Physics in Medicine
Ernest Rutherford (1871-1937)
Pierre Curie (1859-1906) Marie Curie (1867-1934)
Wilhelm Conrad Roentgen (1845-1923)
14
(No Transcript)
15

16

17

18

19

20

21
Ionizing Radiation
Food Preservation Medical Sterilization Medical
and Industrial X-rays Isotope Production Nuclear
Medicine Radiotherapy Nuclear Power Sewage
Treatment Artificial Lighting Smoke Detectors
22
The Electromagnetic Spectrum
23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
(No Transcript)
27
(No Transcript)
28
(No Transcript)
29
(No Transcript)
30
Average Annual Effective Dose to a North American
Source Average Annual Effective
Dose Equivalent (µSv) Inhaled (Radon and
Decay Products) 2000 Other Internally
Deposited Radionuclides 390 Terrestrial
Radiation 280 Cosmic Radiation 270 Cosmog
enic Radioactivity 10 Rounded total from
Natural Source 3000 Rounded total from
Artificial Sources 600 Total 3600
31
Natural Radioactivity in Your Body
Nuclide Total Mass of Nuclide Total Activity of
Nuclide Daily Intake of Found in the Body
Found in Body Nuclide Uranium 90
µg 1.1 Bq 1.9 µg Thorium 30 µg 0.11 Bq 3
µg Potassium-40 17 mg 4.4 kBq 0.39
mg Radium 31 pg 1.1 Bq 2.3
pg Carbon-14 95 µg 15 kBq 1.8
µg Tritium 0.06 pg 23 Bq 0.003
pg Polonium 0.2 pg 37 Bq 0.6 µg
32
Size of Critical Target DNA
Human Cell Nucleus
Yeast Cell
33
Comparative Radiosensitivity of Living Organisms
Factors that Influence LD50 Biological and
Physical
34
Critical Target is DNA
Cell
Nucleus contains DNA
DNA double stranded helix
DNA is packaged on chromosomes
35
Radiation Biology
LD/50 4 Gy 4 Gy 67 calories 67 calories 3
ml sip of 60C coffee
30-100 Trillion Cells at Risk

• Different Cell Types
• Different Cell Cycle
• Different Cell Targets