Radiation Effects in Body Tissues

DIAGNOSTIC RADIOGRAPHY · NTA LEVEL 4 · SEMESTER ONE

Radiation Effects in Body Tissues

CRT04106 · Radiation Sciences

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Radiation Effects in Body Tissues

RADIATION SCIENCE

CHAPTER 3

  • Cell chemical composition
  • Cell differentiation
  • Radiation damage at cellular level
  • Patient age and gender in radiation effects
  • Radiation in Tissue
  • When ionizing radiation (X-rays, gamma rays, particles)
  • interacts with tissue, its biological effects depend on;
  • chemical composition of cells
  • their level of differentiation
  • mechanisms of damage at the cellular level
  • Levels Of Structural Organization of a Human Body About cell
  • A cell is the basic structural and functional unit of
  • living organisms. So when you define cell properties you
  • are in fact defining the properties of life.
  • The activity of an organism depends on both the
  • individual and the collective activities of its cells.
  • Continuity of life has a cellular basis. ✓ Cell Chemical Composition
  • Inorganic compounds
  • o Are compounds which lack carbon and have a simple
  • structure.o Includes;
  • Water, salts, acids and bases.
  • o Water is the most abundant and important inorganic
  • compound in living material. It makes up 60–80% of
  • the volume of most living cells.
  • o Their molecules have only a few atoms and cannot be
  • used by cells to perform complicated biological
  • functions
  • Organic compounds (~20–30%)
  • o Are relatively large carbon-based molecules and
  • have unique characteristics that allow them to carry
  • out complex biological functions.
  • o Includes;
  • carbohydrates, lipids, proteins, nucleic acids, and

adenosine triphosphate (ATP).✓ Cell Propagation

  • Cells propagate (increase in number) through division.❖There are two types of human cells in the body;
  • Germ cells
  • ii. Somatic cells
  • Germ cells
  • These are special cells that are involved in sexual
  • reproduction.
  • These are; – Sperms in males
  • Eggs (ova) in females
  • Division of germ cells is called meiosis and involves two
  • fissions of the nucleus giving rise to four sex cells, each
  • possessing half the number of chromosomes of the
  • original germ cell.Somatic cells
  • These are all other cells in the body that are not
  • involved in reproduction.
  • Division of somatic cells is called mitosis and results in
  • two genetically identical daughter cells.
  • When a somatic cell divides, two cells are produced each
  • carrying a chromosome complement identical to that of
  • the original cell. New cells themselves may undergo further division and
  • the process continues producing a large number of
  • progenies.
  • 𝐍𝐁; Mitosis results in identical cells. This alone is not
  • going to result in different body cells with different
  • functions.
  • To achieve different cells performing different
  • functions in the body, cells also undergo cell
  • differentiation.✓ Cell Differentiation
  • Definition
  • Cell differentiation is the biological process
  • unspecialized cell (like a stem cell) develops into a
  • specialized cell type with distinct structures and
  • functions (e.g., muscle cell, nerve cell, red blood cell).
  • Somatic cells are classified as:
  • Stem cells
  • Are special human cells that are able to
  • develop into many different cell types.
  • ii. Transit cells
  • Which are cells in movement to another
  • population and have properties intermediate
  • between stem and mature cells.
  • iii. Mature cells,
  • Which are fully differentiated and do not exhibit
  • mitotic activity.
  • Examples of Differentiated Cells
  • Erythrocytes (RBCs): Specialized to transport oxygen
  • (contain hemoglobin, lack nucleus).
  • Neurons: Specialized for transmitting impulses (long
  • axons, dendrites).
  • Muscle cells: Specialized for contraction (contain actin
  • and myosin).
  • Epithelial cells: Specialized for protection, secretion, and
  • absorption.
  • Importance of Cell Differentiation
  • Creates diversity of cell types in the body (over 200 in
  • humans).
  • Enables formation of tissues and organs.
  • Crucial for growth, repair, and healing.
  • Malfunction of differentiation can lead to cancers and
  • developmental disorders.✓ Cell Cycle
  • Cell cycle is a series of events that a cell passes
  • through from the time it was produced to its death.
  • It is the growth and division of a single cell into
  • daughter cells and duplication (replication).
  • In prokaryotic cells, the cell cycle occurs
  • termed binary fission but in eukaryotic cells, cell cycle
  • can be divided into two periods namely;
  • a)Interphase
  • b)Mitosis
  • Interphase
  • These is the first phase that prepare a cell for division.
  • During this period a cell grows, accumulate nutrients
  • needed for mitosis and duplicate its DNA.
  • Interphase consists of three stages namely
  • G1 (Pre -synthetic phase)
  • S (DNA synthesis phase)
  • G2 (Pre mitotic phase)
  • Mitotic phase
  • Mitotic phase involves division of cell to produce two
  • daughter cells.❖Mitosis involves four stages
  • Prophase
  • Metaphase
  • Anaphase
  • Telophase
  • Time between successive divisions (mitoses) is called cell
  • cycle time.
  • Cell cycle time for mammalian cells is of the order of 10 –
  • 20 hours:
  • S phase is usually in the range of 6 – 8 hours.
  • M phase is less than 1 hour.

G2 is in the range of 2 – 4 hours.

G1 is in the range of 1 – 8 hours.❖Cell cycle time for stem cells in certain tissues is up to 10 days.

  • In general, cells are most radio-sensitive in the M and G2
  • phases, and most radio-resistant in the late S phase.
  • Cell cycle time of malignant cells is shorter than that of
  • some normal tissue cells, but during regeneration after
  • injury normal cells can proliferate faster.✓ Radiosensitivity
  • Radiosensitivity refers to how sensitive a cell is to
  • radiation damage
  • o Cells are more radiosensitive if they are:
  • 1.Actively dividing (high mitotic rate).
  • 2.Undifferentiated (immature).

3.Have a long-life span (young age).

• Highly Radiosensitive Cells

  • o Stem cells, bone marrow cells, lymphocytes,
  • spermatogonia, basal cells of skin, intestinal crypt
  • cells.
  • Moderately Radiosensitive Cells
  • o Endothelial cells, fibroblasts, salivary gland cells,

growing cartilage and bone cells.

• Radioresistant Cells

  • o Nerve cells, muscle cells, fully differentiated
  • connective tissue.✓ Radiation Damage at Cellular Level

Basic Concept

  • When ionizing radiation (X-rays, γ-rays, particles) passes
  • through a cell, it interacts with atoms and molecules,
  • causing ionization and excitation.
  • This leads to molecular changes, especially in water and
  • DNA.
  • The biological effects depend on the type of radiation,
  • dose, dose rate, and radiosensitivity of the cell.
  • Review of types of radiation
  • Radiation is classified into two main types:
  • 1.Non-ionizing radiation (cannot ionize matter).
  • 2.Ionizing radiation (can ionize matter).
  • Ionizing radiation contains two major categories
  • 1.Directly ionizing radiation (charged particles).
  • eg. electrons, protons, alpha particles, heavy ions.
  • 2.Indirectly ionizing radiation (neutral particles).
  • photons (x rays, gamma rays), neutrons.Linear Energy Transfer
  • When ionizing radiations traverse through matter, they
  • lose energy gradually through various interaction
  • processes along the length of their path.
  • In radiobiology linear energy transfer (LET) is defined as
  • the amount of energy that an ionizing particle transfers
  • to the material per unit distance.
  • LET focuses attention on the linear rate of energy
  • absorption by the absorbing medium as the radiation
  • traverses the medium.
  • LET essentially indicates the quality of different types of
  • radiation and is important because the biological effect
  • of a radiation (its relative biological effectiveness, RBE)
  • depends on its average LET.
  • The SI unit of LET is kiloelectron volt per micrometer.
  • Types of Radiation Based on Linear Energy Transfer
  • There are two types
  • 1.Low LET radiation
  • 2.High LET radiation
  • 1.High LET radiation
  • This is a type of ionizing radiation that deposit a large
  • amount of energy in a small distance.
  • High LET characteristics include; high dense, limited
  • penetration, more effective in causing DNA damage, High
  • biological effectiveness
  • eg. Neutrons, alpha particles and beta particles.
  • 2.Low LET radiation
  • This is a type of ionizing radiation that deposit less
  • amount of energy along the track ie. have inadequate
  • ionizing events.
  • Characteristics of low LET radiation include; less dense
  • iionization, more penetrative, indirect DNA damage, low
  • biological effectiveness.
  • eg X-ray and gamma rays
  • High vs low LET Radiations
  • High LET radiations are more destructive to biological
  • material than low LET radiations.
  • The localized DNA damage produced
  • produced by high LET radiations is difficult to repair than
  • the diffuse DNA damage caused by the sparse ionization
  • from low LET radiations.High LET radiations result in lower cell survival per
  • absorbed dose than low LET radiations.
  • The high LET radiation is aimed at effectively killing of
  • tumor cells while minimizing dose to normal tissues to
  • prevent toxicity.
  • Mechanisms/ Pathways of Cell Damage
  • Direct Action
  • Radiation directly strikes critical targets (mainly DNA).
  • Causes ionization or breakage of molecular bonds.
  • Indirect Action
  • Radiation ionizes water molecules (which make up ~70–
  • 80% of the cell).
  • Produces free radicals (e.g., hydroxyl radical •OH,
  • hydrogen radical •H).
  • These reactive species damage DNA, proteins, and
  • membranes.
  • This is the most common pathway for X-ray and γ-ray
  • damage.3. Types of Cellular Damage
  • 1.DNA Damage
  • o Strand breaks (single or double).
  • o Base modifications.
  • o Chromosome aberrations (deletions, translocations,
  • dicentrics).
  • o Can lead to mutation, apoptosis, or carcinogenesis.
  • 2.Membrane and Organelle Damage
  • o Lipid peroxidation damages cell membranes.
  • o Mitochondrial dysfunction affects energy production.
  • o Lysosomal rupture may release digestive enzymes.3.Protein Damage
  • o Denaturation or cross-linking of proteins.
  • o Enzyme inactivation → metabolic disturbances.
  • Cellular Outcomes of Radiation Damage
  • a)Repair: Cell successfully repairs DNA (enzymatic repair
  • mechanisms).
  • b)Misrepair:
  • If the DNA is not repaired correctly, mutations may
  • persist
  • This altered cell can potentially lead to development of
  • cancer over time.
  • The risk of cancer is a long-term risk, probabilistic
  • effect.
  • c)Cell death:
  • If the damage is too extensive to be repaired, the cell
  • can die.
  • Apoptosis (programmed cell death, active process of
  • cellular self-destruction).
  • Mitotic death (cell fails to complete the cell division
  • cycle, leading to death).

NB; Extensive cell death in a tissue can impair its function and potentially lead to organ failure.d)Senescence: Cell survives but loses ability to divide.

Factors Influencing Cellular Radiation Damage

  • Cell type: Rapidly dividing, undifferentiated cells (e.g.,
  • bone marrow, GI lining, gonads) are more radiosensitive.
  • ii. Cell cycle stage: Cells are most sensitive in G2/M phase,
  • more resistant in late S phase.
  • iii. Oxygen effect: Presence of oxygen enhances free radical
  • formation (oxygen enhancement ratio).
  • iv. Radiation quality: High LET (linear energy transfer)
  • radiation (e.g., α-particles) causes more direct damage
  • than low LET (X-rays).✓ Patient Age and Gender in Radiation Effects
  • Age and Radiation Effects
  • Children and Infants
  • More radiosensitive than adults.
  • Reasons:
  • o Higher proportion of dividing/undifferentiated cells
  • (active growth).
  • o Longer life expectancy → more time for late effects
  • (e.g., cancer, genetic mutations) to manifest.
  • o Organs are smaller → a given dose affects a larger
  • fraction of the body.
  • Clinical significance:
  • o Extra care in pediatric radiology.
  • o Use of ALARA principle (As Low As Reasonably
  • Achievable).
  • o Preference for non-ionizing imaging (ultrasound,
  • MRI) when possible.
  • Adults
  • Radiosensitivity decreases with age because:
  • o Cells are more differentiated.
  • o Slower mitotic activity.
  • However:
  • o Certain tissues (e.g., gonads, thyroid, breast) remain
  • sensitive.
  • Elderly
  • Less radiosensitive overall.• Shorter life expectancy → reduced probability of longterm (stochastic) effects like cancer.
  • More prone to deterministic effects (tissue reactions) if
  • exposed to high doses due to reduced repair capacity.
  • Gender and Radiation Effects
  • Female Sensitivity
  • On average, women have slightly higher lifetime risk of
  • radiation-induced cancer than men.
  • o Example: breast and ovarian tissues are highly
  • radiosensitive.
  • o Thyroid cancer is more common in women.
  • Pregnancy considerations:
  • o Embryo/fetus is extremely radiosensitive, especially
  • during organogenesis (weeks 2–8).
  • o Risks include congenital malformations, growth
  • retardation, mental impairment, and childhood
  • cancers.
  • o Radiation protection guidelines require pregnancy
  • screening before certain exams.
  • Male Sensitivity
  • Testes (especially spermatogonia) are highly
  • radiosensitive.
  • High doses can cause temporary or permanent sterility.
  • Male gonadal exposure also carries hereditary risks
  • (genetic mutations passed to offspring).3. Combined Age and Gender Considerations
  • Group Sensitivity to

Radiation

Key Clinical

  • Implications
  • Infants/Children Very high Prefer nonionizing
  • imaging;
  • minimize
  • dose strictly
  • Women of
  • childbearing
  • age
  • High concern
  • (due to breast,
  • ovaries,
  • pregnancy risk)
  • Screen for
  • pregnancy;
  • shield
  • gonads;
  • justify every
  • exam
  • Pregnant
  • women
  • Extremely high
  • concern (fetal
  • exposure)
  • Use
  • alternative
  • imaging
  • when
  • possible;
  • follow strict
  • dose limits
  • Men
  • (reproductive
  • age)
  • Moderate
  • (testicular
  • radiosensitivity)
  • Protect
  • gonads with
  • lead
  • shielding
  • Elderly Lower long-term
  • risk
  • Late
  • stochastic
  • risks less significant,
  • but tissue
  • tolerance
  • lower
  • Summary
  • Age: Younger = more radiosensitive, higher cancer risk,
  • longer time for effects to appear.
  • Gender: Females slightly more radiosensitive overall;
  • reproductive organs (testes/ovaries) need special
  • protection.
  • Clinical practice: Always apply justification, optimization
  • (ALARA), and protection strategies tailored to patient age

and gender.

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