Week 07 — Biological Effects of Radiation

CLO Covered: CLO-2 — Analyze the interaction of radiation with biological tissues

BS: Medical Physics

Section Topic
This week focuses on how ionizing radiation causes biological damage at molecular, cellular,
tissue, and whole-body levels, and how these effects are modeled and applied in clinical
radiotherapy.

The emphasis is on:

• Mechanisms of DNA damage

• Deterministic vs stochastic effects
• Cell survival modeling
• Oxygen effect and radio sensitivity
• Clinical implications

Learning Outcomes of Week 07

After completing this lecture, students should be able to:

1. Explain the stages of radiation action from physical to biological phase.

2. Distinguish between direct and indirect radiation damage.
3. Describe types of DNA damage and repair mechanisms.
4. Differentiate deterministic and stochastic effects with examples.
5. Interpret cell survival curves using the linear-quadratic model.
6. Explain Relative Biological Effectiveness (RBE).
7. Analyze the oxygen enhancement effect.
8. Evaluate radiation risk in clinical and accidental exposure scenarios.
9. Apply radiobiological principles in treatment planning decisions.

1. Stages of Radiation Action

Radiation effects occur in four stages.

1. Physical Stage (10⁻¹⁵ s)

• Energy deposition
• Ionization
• Secondary electron production

This stage depends on LET and radiation type.

2. Physicochemical Stage (10⁻¹² s)

Water radiolysis begins:

Reactive species form:

• OH (hydroxyl radical)
• H•

These radicals are chemically unstable.

3. Chemical Stage (Microseconds–Seconds)

Free radicals attack:

• DNA
• Proteins
• Lipids

Damage is fixed or reversible depending on repair success.

4. Biological Stage (Minutes–Years)

Cellular responses include:

• DNA repair
• Apoptosis
 • Mutation
• Carcinogenesis

Long-term outcomes may take years.

3. Types of DNA Damage

(i) Direct DNA Damage
 Mechanism: Direct interaction between a pathogen (e.g., ionizing radiation, UV) and the DNA molecule.

 Action: The radiation photon or electron causes ionization of atoms within the DNA structure, resulting
in physical/chemical changes.

 Effects: Includes single-strand breaks (SSBs), double-strand breaks (DSBs), and base modifications.

 Examples: UV-B light causing pyrimidine dimers, high-LET radiation hitting DNA.
 (ii) Indirect DNA Damage
 Mechanism: Radiation interacts with surrounding water molecules (H20) in the cell, rather than
the DNA itself.

 Action: Causes radiolysis of water, producing highly reactive free radicals, such as hydroxyl
radicals (OH-) and hydrogen atoms (H+).
 Effects: The free radicals travel to the DNA and attack it, causing oxidative damage, base
alterations, and breaks.

 Context: This is the primary method of damage for low-LET radiation (X-rays, gamma rays).

4
• Base damage
• Single strand break (SSB)
• Double strand break (DSB)
• Clustered lesions

DSB is the most lethal type.

4. DNA Repair Mechanisms

Non-Homologous End Joining (NHEJ)

Fast but error-prone.

Homologous Recombination (HR)

Accurate but limited to certain cell cycle phases.

Failure of repair leads to chromosomal aberrations.

5. Chromosomal Aberrations
2. Types of Chromosomal Aberrations

A. Structural Aberrations
4

Deletion
Loss of a chromosome segment.

Translocation
Segment moves to another chromosome.
Dicentric chromosome
Two centromeres formed after misjoining.
→ Highly specific marker of radiation exposure.

Inversion
Segment flips 180° within same chromosome.

Ring chromosome
Ends join forming a ring.

B. Numerical Aberrations

• Aneuploidy – Gain or loss of chromosome

• Polyploidy – Entire extra chromosome sets

Less specific to radiation compared to dicentrics.

3. Classification by Stability

Unstable aberrations
Dicentrics, rings
→ Cell dies after few divisions
→ Used for acute radiation dose estimation

Stable aberrations
Translocations
→ Persist for years
→ Used in long-term exposure studies

4. Detection Methods
4
Dicentric Chromosome Assay (DCA)
Gold standard in radiation biodosimetry.

FISH (Fluorescence In Situ Hybridization)

Detects stable translocations.

G-banding cytogenetics
Classical karyotyping.

5. Dose–Response Relationship

• Aberrations increase with radiation dose.

• Follows linear-quadratic model:

Y=αD+βD^2

Where:
Y = aberration frequency
D = dose

Low dose → linear

High dose → quadratic component significant

6. Importance in Medical Physics

Radiotherapy:
• Predict normal tissue damage
• Estimate accidental overexposure

Diagnostic Radiology:
• Monitor occupational exposure

Radiation Accidents:
• Biological dose assessment

Research:
• Evaluate radioprotectors

7. Key Concepts for Exam

• Double-strand break = main cause
• Dicentric = radiation signature
• High LET → clustered damage
• Stable vs unstable aberrations
• Linear-quadratic dose response
• Used in biodosimetry

6. Deterministic Effects
Characteristics:

• Threshold dose exists

• Severity increases with dose

Examples:

• Skin erythema (~2 Gy)

• Cataracts (~0.5–2 Gy)
• Radiation sickness (>1 Gy whole body)

Below threshold → no effect.

7. Stochastic Effects
A stochastic effect is a random biological effect of radiation where, In medical physics,
stochastic effects refer to radiation-induced cancers and genetic mutations that may occur
after diagnostic or therapeutic exposure.

Ionizing radiation → DNA mutation (often single-cell mutation) → if repair fails → possible
cancer years later.

Characteristics:

• No threshold assumed
• Probability increases with dose
• Severity independent of dose

Main examples:
• Cancer
• Genetic mutations

Risk modeled using Linear No Threshold (LNT) model.

8. Dose–Response Models

Models:
• Threshold model (deterministic)
• Linear model
• Linear-quadratic model

9. Cell Survival Curve

Linear-Quadratic
equation:

Where:

S = survival fraction
D = dose
α = single-event damage
β = double-event damage

High LET → more linear curve.

10. Oxygen Enhancement Effect

Oxygen enhances radiation damage.
OER:

Typical value for X-rays ≈ 2–3.

Hypoxic tumors are more resistant.

11. Radio sensitivity of Tissues

Most sensitive:

• Bone marrow
• Intestinal lining
• Gonads

Most resistant:

• Muscle
• Nerve

Rapidly dividing cells are more sensitive.

12. Acute Radiation Syndrome

Whole-body exposure effects:

1–2 Gy → mild
2–6 Gy → hematopoietic syndrome

6 Gy → gastrointestinal syndrome
20 Gy → CNS syndrome

Symptoms include nausea, infection, and hemorrhage.

13. Fractionation in Radiotherapy
Radiotherapy delivered in small fractions.

Benefits:

• Normal tissue repair

• Tumor reoxygenation
• Reduced complications

Four R’s:

Repair
Reoxygenation
Redistribution
Repopulation

14. Case Study — Step-by-Step

Scenario:
Patient accidentally receives 8 Gy instead of 2 Gy in one session.

Step 1 — Physical Stage

Large energy deposition → increased ionization.

Step 2 — Chemical Stage

Excess free radicals formed.

Step 3 — DNA Damage

High number of DSBs.

Step 4 — Survival Calculation

Using LQ model:
Higher D → survival fraction sharply reduced.

Step 5 — Tissue Response

Threshold exceeded → deterministic skin injury likely.

Step 6 — Long-term Risk

Increased probability of secondary cancer.

15. Clinical Decision Example

Tumor near spinal cord.

Comparison:

X-ray therapy → larger normal tissue dose.

Proton therapy → localized Bragg peak.

Decision based on:

• LET
• RBE
• Dose distribution
• Biological tolerance

Final Integrated Understanding

Week 07 completes the chain:

Radiation → Ionization → DNA damage → Cellular response → Tissue effect → Clinical

outcome.

You now understand both the physics and biological consequence of radiation interaction.
Week 07 – Biological Effects of Radiation

1.

Ionizing radiation causes biological damage mainly by:

A) Heating tissue
B) Ionizing atoms
C) Stretching cells
D) Increasing blood flow

2.

The primary target molecule for radiation damage is:

A) Lipid
B) Protein
C) DNA
D) Glucose

3.

The physical stage of radiation action lasts:

A) Hours
B) Minutes
C) Femtoseconds
D) Days

4.

Water radiolysis produces mainly:

A) Oxygen gas
B) Hydroxyl radicals
C) Helium
D) Nitrogen

5.

Indirect radiation damage occurs through:

A) Direct DNA ionization
B) Free radical formation
C) Mechanical stress
D) Heat transfer

6.

High LET radiation produces:

A) Sparse ionization
B) Dense ionization tracks
C) No DNA damage
D) Only single strand breaks

7.

A double strand break is more serious than a single strand break because:
A) It is easier to repair
B) It affects both DNA strands
C) It increases oxygen
D) It reduces mutation

8.

Non-homologous end joining is considered:

A) Accurate
B) Error-prone
C) Impossible in humans
D) Instantaneous

9.
Homologous recombination requires:
A) Oxygen
B) Sister chromatid
C) Neutrons
D) Magnetic field

10.

Deterministic effects have a:

A) Linear response
B) Threshold dose
C) No threshold
D) Random severity

11.

Skin erythema is an example of:

A) Stochastic effect
B) Deterministic effect
C) Genetic mutation
D) Indirect action

12.

Stochastic effects mainly refer to:

A) Burns
B) Cancer risk
C) Hair loss
D) Immediate death

13.

In stochastic effects, severity is:

A) Dose dependent
B) Independent of dose
C) Zero
D) Constant
14.

The Linear No Threshold model assumes risk:

A) Decreases with dose
B) Is zero below threshold
C) Increases linearly with dose
D) Is constant

15.

Relative Biological Effectiveness increases with:

A) Decreasing LET
B) Increasing LET
C) Decreasing dose rate
D) Cooling

16.

High LET radiation is usually:

A) Less damaging
B) More damaging per unit dose
C) Harmless
D) Only thermal

17.

Oxygen increases radiation damage by:

A) Blocking radicals
B) Fixing free radical damage
C) Reducing ionization
D) Cooling cells

18.

The Oxygen Enhancement Ratio is usually:

A) Less than 1
B) Equal to 1
C) Between 2 and 3 for X-rays
D) Above 10

19.

Rapidly dividing cells are generally:

A) More radiosensitive
B) More resistant
C) Unaffected
D) Immune

20.

Bone marrow is considered:

A) Resistant
B) Highly sensitive
C) Neutral
D) Unaffected

21.

Muscle tissue is generally:

A) Highly sensitive
B) Moderately sensitive
C) Resistant
D) Most sensitive

22.

Acute Radiation Syndrome occurs after:

A) Very low dose
B) Whole-body high dose
C) MRI exposure
D) Ultrasound
23.

The hematopoietic syndrome affects:

A) Brain
B) Bone marrow
C) Liver
D) Kidney

24.

Clustered DNA damage is typical of:

A) Low LET
B) High LET
C) Ultrasound
D) Light

25.

Free radicals mainly attack:

A) Water
B) DNA
C) Magnetic fields
D) Photons

26.

The Linear-Quadratic model equation is:

A) S = D²
B) S = e⁻(αD + βD²)
C) S = α + β
D) S = D

27.

In the LQ model, α represents:

A) Double-hit effect
B) Single-hit damage
C) Oxygen ratio
D) Dose rate

28.

β represents:
A) Single-event damage
B) Double-event interaction
C) Repair rate
D) Mutation probability

29.

As dose increases, survival fraction:

A) Increases
B) Decreases
C) Remains same
D) Becomes zero instantly

30.

High LET survival curves are generally:

A) Curved
B) Linear
C) Flat
D) Random

31.

Fractionation in radiotherapy allows:

A) Increased mutation
B) Repair of normal tissue
C) Higher toxicity
D) No benefit

32.
The Four R’s include all except:
A) Repair
B) Reoxygenation
C) Redistribution
D) Reflection

33.

Radiation-induced mutation results from:

A) Perfect repair
B) Misrepair
C) No DNA damage
D) Oxygen absence

34.

Cataract formation is classified as:

A) Stochastic
B) Deterministic
C) Genetic
D) Acute

35.

Cancer after radiation exposure is:

A) Deterministic
B) Stochastic
C) Immediate
D) Threshold-based

36.

The most critical cellular component for radiation damage is:

A) Cytoplasm
B) Mitochondria
C) DNA
D) Ribosome
37.

Ionization density increases when:

A) LET decreases
B) LET increases
C) Dose decreases
D) Temperature increases

38.

Hypoxic tumor cells are:

A) More sensitive
B) More resistant
C) Unaffected
D) Destroyed immediately

39.

Double strand breaks may lead to:

A) Faster repair
B) Chromosomal aberrations
C) Reduced damage
D) Energy loss

40.

Latency period refers to:

A) Immediate symptoms
B) Time between exposure and effect
C) Repair time
D) Dose delivery time

41.

High doses primarily cause:

A) Only stochastic effects
B) Deterministic effects
C) No biological response
D) Genetic inheritance only

42.

Apoptosis occurs when:

A) Repair is complete
B) Damage is severe
C) Dose is zero
D) LET is minimal

43.

The gastrointestinal syndrome occurs at doses above approximately:

A) 0.1 Gy
B) 1 Gy
C) 6 Gy
D) 0.01 Gy

44.

Radiobiology links radiation physics to:

A) Astronomy
B) Clinical medicine
C) Thermodynamics
D) Mechanics

45.

Indirect damage is more common with:

A) Alpha particles
B) X-rays
C) Heavy ions
D) Neutrons
46.

RBE compares biological effectiveness relative to:

A) Alpha particles
B) Neutrons
C) X-rays
D) Ultrasound

47.

The probability of stochastic effects depends on:

A) Severity
B) Dose
C) Oxygen only
D) Temperature

48.

Chromosomal aberrations indicate:

A) Perfect repair
B) Radiation exposure
C) No damage
D) Oxygen effect

49.

The survival fraction becomes very small at:

A) Low dose
B) High dose
C) Zero dose
D) Diagnostic dose only

50.

Understanding biological effects is essential for:

A) ECG
B) Radiotherapy planning
C) Ultrasound imaging
D) MRI contrast