Radiation Biology

RADL 70

Kyle Thornton

Definition of Radiation Biology

Joins two branches of science to study the effects of radiation upon living matter Radiation physics

The spread of energy through space Biology

The study of living organisms

Most effects begin at the cellular level All radiation injuries to tissue, organs, fetus, and

entire body began from an injury to a cell

How Does Ionizing Radiation Do Harm? It damages by removing electrons the

atoms that compose the molecular structures of living systems

X and gamma rays can transfer energy to orbital electrons in their path

Alpha particles strongly attract negative electrons as they pass by

This alters the chemical bonds of the atom, changing its composition or structure

Different types of atoms unite through chemical bonds to form molecules

Molecules have specific functions Altering the structure of the atom alters

the moleculecular structure and its function

Linear Energy Transfer

The average amount of energy deposited per unit length of travel

Measured in units of keV per micron The amount of ionization produced is

affected by the amount of energy absorbed Chemical and biological effects are

determined by the degree of ionization that takes place within the tissue

Linear Energy Transfer

Low LET radiations From x or gamma rays

Short wavelength, high energy waves Sparsely ionizing Randomly interact They do not give up their energy quickly Damage is usually caused indirectly

Free radicals are formed Occasionally may cause single-strand breaks in one side of

the DNA ladder Damage is usually sublethal

Repair enzymes reverse the damage

Linear Energy Transfer

High LET radiationFrom particles that do possess mass and

chargeAlpha particles, particles released from

interactions between neutrons and atomsLose energy more rapidly than x or gamma raysProduce more ionization per unit length of travelTheir energy is exhausted sooner than that of

an x or gamma ray

Linear Energy Transfer

Radiation of a high LET is far more likely to do damage than that of a low LET

Damage potential is greatest when a radionuclide has been ingested, planted, inhaled, or injected into the body

The damage done by high LET is usually irreparable

High LET radiation is far more likely to interact with DNA than low LET radiation

Electron/Alpha Particle Damage Comparison

Relative Biological Effectiveness Biologic damage increases as LET

increases RBE is the ability of radiation with different

LET to produce a biologic reaction

Oxygen Enhancement Ratio

The ratio of radiation damage done when oxygen is present compared to the amount when it is not

Cells that are normally hypoxic are less responsive to cells are that are highly oxygenated

This is only important when high doses outside the realm of diagnostic are used

This impact is very important in radiation therapy procedures

Direct Action

Biologic damage occurs from interaction between radiation and a master molecule DNA, RNA, enzymes, and

proteins Occurs from photoelectric and

Compton interaction This results in breakage of the

macromolecule’s chemical bonds This will result in a malfunction of

that particular molecule This sets off a biologic domino

effect

Indirect Action

The byproduct of radiation interacted with the macromolecule, not the radiation itself

Radiolysis of water is one of the main precursors of indirect action

Indirect Action

Indirect Action: Radiolysis of Water

X-ray photons are highly likely to interact with water molecules in the body

This interaction creates an ion pair A water molecule with a

positive charge HOH+ An electron - e-

One of several reactions might occur

Reaction I

The positively charged water molecule recombines with an electron

A stable water molecule is reformed No damage is done

Reaction II

The electron joins with a water molecule A negative water ion is formed The positive and negative water molecules are

unstable These can break apart into smaller molecules Free radicals can be formed by this breakup

These are atoms that have no net electrical charge These objects are highly reactive and can do

cellular damage

Reaction III

Two of these free radicals can recombine to form hydrogen peroxide

This is highly toxic to a cell About two-thirds of all biologic damage is

caused by the two latter reactions

Another way to look at it…

News Flash!!!

Midterm exam takes place next meetingBe ready

Effects on DNA Macromolecules Point mutation

Ionizing radiation that ruptures the chemical bond of a macromolecule severing one of the sugar-phosphate chain siderails of the DNA ladder (Single-strand break)

Gene mutations may result These can occur with low-LET radiationRepair enzymes can reverse this damage

Double Strand Breaks

One or more breaks in each of the two sugar-phosphate chains

Not repaired as easily as single strand breaks

More common with high LET radiation

Cleaved Chromosomes

Two interactions hit on each side of the sugar phosphate chain

The macromolecule is broken in two Each new portion contains an unequal

amount of genetic material This chromosome can then divide into

defective daughter cells This loss or change is known as a mutation

Let’s play mutation identification!

Effects of Ionizing Radiation Upon Chromosomes If chromosomes are broken, two or more

fragments are produced Each fragment has a fractured extremity These can join to another fractured

extremity These new formations are known as an

aberration

Restitution – No Visible Damage

Deletion

Broken-endRearrangement

Broken End Rearrangement

DNA Mutations

Target Theory

Cell death will occur if the master molecule in that cell is inactivated by radiation exposure

This theory is used to explain cell death and nonfatal cell abnormalities caused by radiation exposure

Target Theory

Characteristics of Radiation Mutation If the mutation is genetic, it may be expressed in

future generations If it is somatic, it holds possible consequences for

the individual only Radiation effects are non-specific There are no radiounique effects Most mutations are undesirable Mutagenic effects are probably cumulative A threshold exists

Cellular Effect of Irradiation

Instant deathOccurs when a volume is irradiated with 1000

Gray of x or gamma ray in a period of seconds or a few minutes

Radiation doses this high do not occur in the diagnostic or therapeutic ranges

Cellular Effect of Irradiation

Reproductive DeathOccurs from a dose of 1 – 10 GrayThe cell does not die, but becomes sterileThe cell will continue to metabolize and

synthesize nucleic acids and proteinsTransmission of damage to future generations

is prevented

Cellular Effect of Irradiation

Interphase DeathDepends upon the radiosensitivity of the cellThis death interrupts a programmed

occurrence in normal development

Cellular Effect of Irradiation

Mitotic DeathOccurs when the cell dies after one or more

divisionsCan occur from very small doses

Cellular Effect of Irradiation

Mitotic DelayCan occur from a dose of as little as 1 radThe cell fails to divide on time

Interference of functionThis can be temporary or permanent The cell can recover and continue to function

if repair enzymes are able to fix the damage

Cell Radiosensitivity

Cells vary in their degree of radiosensitivity Radiosensitive cells include basal cells of

the skin, intestinal crypt cells, and reproductive cells

Radioinsensitive cells include brain, muscle, and nerve cells

Radiosensitivity varies from one tissue or organ to another

Cell Radiosensitivity

Other factorsLETPresence of oxygen

Cancer cells are often hypoxic Patients often undergo hyperbaric oxygenation to

oxygenate cancer cells This makes them more sensitive to radiation

Law of Bergonié and Tribondeau Experimented on rabbit testicles Their conclusion:

These cells are most radiosensitive by virtue of these factors:

Least maturity Least specialization or differentiation Greatest reproductive activity Longest mitotic phases

True for all cells in the human body

Effects of Radiation on Various Cell Types Blood Cells

Whole body dose of 25 rad (0.25 Gy) produces hematologic depression within a few days

Most blood cells are manufactured in the bone marrow

Radiation causes a decrease in the production of immature blood cells (stem, or precursor cells)

This produces a decrease in the number of mature cells in the bloodstream

The higher the dose, the greater the severity of cell depletion

Radiation and Blood Cells

LymphocytesWhite blood cellsLive for about 24 hours25 rads will depress the number of these cells

in circulating bloodThese are the most sensitive cells in the

human body

Epithelial Tissue

Lines and covers body tissue These cells lie close together Contains no blood vessels Regenerates through mitosis Found in the lining of intestines, mucous lining of

respiratory tract, pulmonary alveoli, and lining of blood and lymphatic vessels

It is constantly regenerated by the body and is very radiosensitive

Muscle Tissue

Contains fibers that affect organ, or body movement

Highly specialized, non-dividing tissue Insensitive to radiation

Nervous Tissue

Conductive tissue – found in the brain and spinal cord

Nerve cells are highly specialized in the adult and do not divide

A single exposure of 5000 rads may lead to death within hours or days

Developing nerve cells are highly radiosensitive in the fetus Irradiation of the fetus can lead to congenital anomalies

Reproductive Cells

These cells are relatively radiosensitive Radiosensitivity depends on cell maturity A radiation dose of 200 rad can cause

temporary sterility for about a year in the male

500 – 600 rads can cause permanent sterility 10 rads can depress the sperm count

Reproductive Cells

Few diagnostic therapy come close to delivering a dose of 10 rads

In the female, ova do not divide constantly Temporary sterility occurs from a dose of

200 rads to the ovaries 500 rads can cause permanent sterility 10 rads may produce menstrual

irregularities

Dose-response Relationship Curves Linear-nonthreshold curve estimates the risk of

associated with low-level radiation Leukemia, breast cancer, and heritable damage are

presumed to follow this curve Leukemia occurrences in Hiroshima and Nagasaki

support the use of this curve This curve somewhat exaggerates the seriousness

of effects at low-level radiation It accurately reflects the effects of high-LET radiation

at higher doses

Dose-response Relationship Curves Linear-threshold curve

Used for nonstochastic effects such as skin erythema and hematologic depression

Non-linear-threshold curveUsed to determine high dose response in

radiation therapy Indicates the existence of a threshold

Threshold Curves

Threshold Curves

The Factors that Determine Somatic and Genetic Damage The quantity of ionizing radiation received The ability of the ionizing radiation to cause

ionization of human tissue The amount of body area exposed The specific body parts exposed

The greatest amount of biologic damage is produced by a large dose of high-LET delivered to a large or radiosensitivity area of the body