Radiation Biology Unit 3 (1/30/2025)

What is radiation biology?

the branch of biology concerned with the effects of ionizing radiation on living systems

What percent of the human body is water?

80%

What is the simplest molecule in the body?

water

List the molecular composition of the body

• 80% water

• 15% protein

• 2% lipids

• 1% carbohydrates

• 1% nucleic acids

• 1% other

What is the chain reaction result of ionizing radiation?

• disruption of molecular bonds

• alter biochemical pathways

• transformation of a cell

• observable effects at the tissue or whole body level

What characteristics determine the extent to which different radiations transfer energy into biologic tissues?

• charge

• mass

• energy

What are 3 radiation transfer determinants?

• LET - linear energy transfer

• RBE - relative biologic effectiveness

• OER - oxygen enhancement ratio

Explain linear energy transfer

• radiation loses energy along its track through a medium (human tissue)

• the average energy deposited per unit length of track

• measured in soft tissue; described in units of KeV/micron

LET is divided into 2 categories:

high LET and low LET

Explain low LET radiation

• short wavelength, high energy

• x-rays, gamma rays, electrons

• have no charge or mass

• sparsely ionizing, interacts randomly along the length of its track

• does not give up all of its energy quickly

• causes damage primarily by indirect action

Explain high LET radiation

• particles that have substantial mass and charge (such as alpha particles)

• lose energy rapidly over a shorter length of track

• produce more ionizations per unit length of travel

• exhaust energy in a shorter path length (cannot travel or penetrate as far)

Does high or low LET deposit more energy per unit of biologic tissue traversed?

high LET

Is high or low LET more destructive to biologic matter?

high LET

When is the greatest risk with high LET radiation?

when internal contamination occurs (implanted, ingested, injected, inhaled)

What does RBE stand for?

relative biologic effectiveness

Explain relative biologic effectiveness (RBE)

• describes the relative capabilities of radiations with differing LETs to produce a particular biologic reaction

• a radiation weighting factor (W_R) is used to calculate the equivalent dose (EqD)

• the W_R values are similar to values of RBE for any particular type of radiation

What is the relationship between LET and RBE?

the ability of ionizing radiation to produce biologic response increases as LET increases (direct relationship)

as LET goes up, RBE goes up

Explain dose protraction

when a dose is delivered continuously but at a lower rate, it is protracted

(x dose delivered over a long period of time is safer than that same dose delivered quickly)

Explain dose fractionation

when radiation dose is delivered at the same dose (Gy) in equal portions at regular intervals

What does OER stand for?

Oxygen Enhancement Ratio

What is oxygen enhancement ratio?

• when in an oxygenated state (aerobic), biologic tissue is more sensitive to radiation than when it is exposed under anoxic or hypoxic conditions

• known as the oxygen effect

• can be described numerically by the OER

• the ratio of radiation dose required to cause a particular biologic response of cells in an oxygen deprived environment to the radiation dose required to cause an identical response under normal oxygenated conditions

What is the OER equation/ratio?

OER = rad dose without oxygen / rad dose with oxygen

Does an increase in oxygen cause more or less biologic damage?

more

(it is a direct relationship)

What is the oxygen fixation hypothesis?

without oxygen, damage produced by indirect action of radiation on biologic molecule may be repaired, but when damage occurs through an oxygen-mediated process, the end result is permanent or fixed

Explain the molecular effects of irradiation

• any visible radiation-induced injuries to living systems at the cellular or organic level always begins with damage at the molecular level

• molecular damage results in the formation of structurally changed molecules that may impair cellular function

All body cells except male and female germ cells are called ___

somatic cells

___ cells are reproductive cells

germ

If radiation damages the germ cells, the damage may be passed on to future generations in the form of ___

genetic mutations

Based on the site of the interaction, the effect of radiation on the cell is classified as either ___

direct or indirect

Explain direct action radiation interactions with cells

• occurs when ionizing radiation interacts directly with vital biologic macromolecules (DNA, RNA, proteins, enzymes)

• results in breakage of the chemical bonds causing abnormal structures, which may lead to inappropriate chemical reactions

Explain indirect action radiation interactions with cells

• a multistage process that involves the production of free radicals that are created by interaction of radiation with water

• the human body consists of 80% water

Match x-ray, alpha, and gamma rays with direct or indirect action

direct: alpha particles

indirect: x-ray and gamma rays

Match high and low LET with direct or indirect action

direct: high LET

indirect: low LET

Is radiolysis a direct or indirect effect?

indirect

What is radiolysis of water?

the dissociation (break down) of water molecules into other products caused by the interaction of radiation with water

Explain the process of radiolysis

• water molecule is struck by radiation and dissociates into 2 ions (an ion pair)

• positive water molecule (HOH⁺) and an electron (e^-)

• these ions are unstable

What are some things that can happen as a result of radiolysis?

• positive water and electron recombine

• electron joins with water molecule creating a negative water molecule

positive and negative water molecules are unstable and will break apart

How are free radicals formed?

• positive water molecule breaks apart to form a hydrogen ion and a hydroxyl radical

  • HOH⁺ → H⁺ + OH*

• negative water molecule breaks apart to form a hydroxyl ion and a hydrogen radical

  • HOH^- → OH^- + H*

What are the end products of radiolysis?

• the formation of an ion pair: hydrogen ion (H⁺) and hydroxyl ion (OH^-)

• the formation of 2 free radicals: hydrogen radical (H*) and hydroxyl radical (OH*)

• interaction with H₂O = H⁺ + OH^- and H* + OH*

What is the best possible outcome after radiolysis (and the formation of free radicals)?

the hydrogen and hydroxyl ions recombine to form a normal water molecule

What is a free radical?

a configuration of a single atom, or, most often, a combination of atoms that are very chemically reactive as a result of the presence of an unpaired electron

The energy from free radicals can break chemical bonds or form ___

toxic bonds

Do free radicals occur in nature?

no; they are a result of some form of interaction

Can free radicals travel through cell membranes?

yes; this allows them to cause damage in areas away from their origin

How long is the lifespan of a free radical?

< 1 millisecond

Approximately two thirds of all radiation induced damage is believed to be caused by ___

the hydroxyl radical (OH*)

A hydroxyl radical may bond with another hydroxyl radical to form ___

hydrogen peroxide (this is poisonous to the cell)

A hydrogen free radical can combine with molecular oxygen to form a ___

hydroperoxyl radical

___ and ___ are the primary substances that produce biologic damage after interaction of water and radiation

hydroperoxyl radical and hydrogen peroxide

Is the damaging action of ionizing radiation direct or indirect?

indirect (in the sense that the radiation is not the immediate cause of injury to the macromolecule)

Explain single strand DNA breaks

the energy transfer can rupture one of the chemical bonds, possibly severing one of the side rails or strands of the ladder-like molecular structures

Single strand break injuries to DNA are called ___

point lesions

Point lesions commonly occur with high or low LET radiation?

low LET

Can damage to the DNA “rail” be fixed?

yes

Can damage to the DNA base pairs be fixed?

no; usually causes gene abnormalities

Explain double strand DNA breaks

• one or more breaks in the sugar phosphate chains

• when 2 hits (one on each side) occur within the same rung

  • if the DNA is cut into 2 pieces, the chromosome itself is broken

  • results in a cleaved or broken chromosome

  • if new chromosome divides, daughter cells will have wrong genetic information

• not repaired as easily as single strand breaks

• often associated with loss of one or more nitrogenous bases

Do double strand DNA breaks commonly occur with high or low LET radiation?

high LET

Define mutation

• changes in genes caused by the loss or change of a nitrogenous base on the DNA change

• alterations of the base sequence within the DNA molecule

• may not be reversible and may generate acute consequences for the cell

• incorrect genetic information will be transferred to one of the daughter cells when the cell divides

Explain covalent cross-linking

• can occur in many different patterns

• crossing between structures

• where break occurs, the broken ends appear sticky and have the ability to adhere to another segment

• unions between atoms by the single sharing of one or more pairs of electrons

What are chromosomal fragments?

• after chromosome breakage, 2 or more chromosomal splinters are produced

• each of these has a fractured extremity (these broken ends are chemically very active and have a strong tendency to adhere to another similar end)

What are some effects of ionizing radiation on chromosomes?

• the broken “fractured” ends may rejoin in their original configuration

• they can fail to rejoin and create an aberration (lesion or abnormality)

• can join other broken ends and create new chromosomes

What are the 2 types of chromosomal anomalies that have been observed at metaphase?

chromosome aberrations and chromatid aberrations

What are chromosome and chromatid aberrations?

chromosome aberrations: occur when irradiation occurs early in interphase before DNA synthesis takes place

chromatid aberrations: occur if irradiated later in interphase, after DNA synthesis

Explain restitution as a consequence to cell from structural changes

• breaks rejoin in their original configuration with no visible damage

• the way ~95% of single chromosome breaks mend

Explain deletion as a consequence to cell from structural changes

• part of the chromosome or chromatid is lost at the next cell division creating an aberration known as an acentric fragment

• results in cell mutation

Explain broken end rearrangement as a consequence to cell from structural changes

a grossly misshapen chromosome may be produced

Explain broken-end rearrangement without visible damage as a consequence to cell from structural changes

chromatids genetic material is rearranged even though the chromosome appears normal (translocation)