RAD 208 Molecular and Cellular Radiation Biology

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

Radiation Biology

Dose Dependent, Response increases with severity of increasing dose

Deterministic

Incidence of radiation response increases with increasing rad dose

Stochastic

a measure of the rate at which energy is transferred from ionizing radiation to soft tissue

Linear Energy Transfer (LET)

What’s the unit for LET

kiloelectron volts (keV) per micron (keV/μm)

Low LET examples?

x-ray & gamma rays

High LET examples

Alpha

As LET of radiation increases, the ability to produce biologic damage also increases This effect is quantitatively described by the

Relative Biologic Effectiveness (RBE)

radiation dose is delivered continuously but at a lower dose rate

Protracted

radiation dose delivered at the same dose in equal portions at regular intervals

Fractionated

Dose protraction and fractionation cause less effect because

time is allowed for intracellular repair and tissue recovery

Biological Factors Affecting Radiosensitivity

Oxygen effect

age

recovery

chemical agents

Hormesis

The ratio of the radiation dose required to cause a particular biologic response of cells or organisms in any oxygen-deprived environment to the radiation dose required to cause an identical response under normally oxygenated conditions.

Oxygen enhancement ratio (OER)

Tissue is more sensitive to radiation when irradiated in

Oxygenated or aerobic state

without oxygen

anoxic

low oxygen

hypoxic

Tissue is more radiosensitive in anoxic or hypoxic conditions

hypoxic

OER is LET dependent. OER is highest for low- LET radiation, with a maximum value of appox. 3 that
decreases to approx. 1 for high- LET radiation

If LET goes up RBE also goes up and vice versa

Why is OER higest with low LET when combined with oxygen compared to High LET

b/c high LET doesn’t need extra destruction since it already has the destructive power even w/out the use of oxygen unlike low LET

Stage in life when a person is most radiosensitive?

Fetal stage and childhood

When are people the least radiosensitive?

adulthood

why are elderly more sensitive to radiation then adults?

b/c they don’t recover as fast so they become more sensitive

Instant death of large numbers of cells occurs when a volume is irradiated with an x-ray or gamma ray dose of approximately 1000 Gyt in seconds or a few minutes

Instant Death

Although the cell does not die when reproductive death occurs, it permanently loses its ability to procreate

Reproductive death

A non-mitotic, or non-division, form of cell death that occurs when cells die without attempting division during the interphase portion of the cell life cycle

Interphase death (Apoptosis)

Mitotic, or genetic, death occurs when a cell dies after one or more divisions. Even relatively small doses of radiation have a possibility of causing this type of cell death.

Mitotic death

Exposing a cell to as little as 10cGy t of ionizing radiation just before it begins dividing can cause mitotic delay, the failure of the cell to start dividing on time. After this delay the cell may resume its normal mitotic function

Mitotic delay

Chemical that makes cells more sensitive

radiosensitizers

have not found human applications but are chemicals that are suppose to protect you from radiation

Radioprotectors

Theory that radiation is good for you

Hormesis

The radiosensitivity of cells is directly proportional to their reproductive activity and inversely proportional to their degree of differentiation. Radiosensitivity of living tissue varies with maturation and metabolism

Law of Bergonie and Tribondeau

Which is the most radiosensitive cell?

Lymphocytes

Aside from Lymphocytes which other cell is highly radiosensitive?

Spermatogonia

Which cells are the least sensitive?

Muscle and Nerve cells

Stems cells are radiosensitive or insensitive?

Radiosensitive

A whole-body dose of how much depresses blood count

25 rad

The ability of ionizing radiation to produce a more intense biologic response in a tissue is NOT related to which of the
following

a decrease in the linear energy transfer

Radiobiologists in research use these curves to establish relationships between radiation and dose-response

Dose-response curve

Using dose curve information obtained can be used to predict the risk of malignancy in human populations that have been

exposed to low levels of ionizing radiation

relationship indicates that the magnitude of a biological effect does not change proportionally with dose, often forming a curve rather than a straight line

non-linear

a straight-line relationship where the biological effect (response) changes proportionally with the amount of exposure (dose)

linear

If the response starts at any place outside of zero?

threshold

if the response starts at zero

nonthreshold

stochastic is what type of dose-response relationship

linear nonthreshold

nonlinear threshold is also known as?

sigmoid line

a localized disruption of a biological molecule's structure (DNA, RNA, or protein), often caused by radiation, resulting in altered function or cell death. Normally happens w/ low LET radiation and typically affect single chemical bonds or base pairs

point lesion

The breakage of the long-chain macromolecule that divides the long, single molecule into smaller ones. Also changes the viscosity of the solution.

Main-chain scission

there are 2 types of main chain scissions:

double strand break but in different nitrogenous base “rungs”

double strand break but in the same rung

Same rung break = clean snap of the chromosome Unequal DNA distribution → faulty daughter cells → cell death or dysfunction

Double-Strand Break in the Same Rung of DNA

Strands of the DNA are broken. Much harder to repair The DNA can separate into pieces. Loss of genetic information (nitrogenous bases) Cell death (lethal damage) Mutations if repaired incorrectly

double strand break but in different nitrogenous base “rungs”

Double strand lesion are more likely to occur with what type of radiation?

High LET

Some macromolecules have side structures that behave as though they have a sticky substance on their ends, and they attach to another macromolecule or to another segment of the same molecule.

crosslinking

Effects on chromosomes

Radiation-induced chromosome breaks in both somatic and
reproductive cells

Chromosomal fragments

Chromosome anomalies

Structural changes in biologic tissue caused by ionizing
radiation

The segmenting of a chromosome due to the breaking of one or both of the sugar–phosphate chains of a DNA ladder-like structure, which is a potential outcome when ionizing radiation interacts with a DNA macromolecule

Chromosome breakage 

chromosome Anomilies 2 type:

chromosome aberration

Deviation from normal development or growth. Lesions that result when irradiation occurs early in interphase, before DNA synthesis takes place.

chromosome aberrations

Deviation from normal development or growth. Lesions that result when irradiation of individual chromatids occurs later in interphase, after DNA synthesis has taken place.

Chromatid aberrations

Consequences to the Cell from Structural Changes in Biologic Tissue

Restitution

Deletion

Broken-end rearrangement

Broken-end rearrangement without visible damage to
the chromatids

the breaks rejoin in their original configuration with no visible damage

Restitution

a part of the chromosome or chromatid is lost at the next cell division, thus creating an aberration known as an acentric fragment which results in a cell mutation.

Deletion

A grossly misshapen chromosome may be produced which results in mutation

Broken-end rearrangement

whereby the chromatid’s genetic material has been rearranged, yet the chromatid appears normal

Broken-end rearrangement without visible damage to
the chromatids

is the study of cell genetics with emphasis on cell chromosomes

Cytogenetics

A cytogenetic analysis of chromosomes may be
accomplished through the use of a chromosome
map called a…. which is a map that consists of a
photograph, or photomicrograph

Karyotype

f a sufficient quantity of …. are affected, entire body processes may be disrupted

somatic cells

If radiation damages the … the damage may be passed on to future generations in the form of genetic mutations

germ cells

biologic damage occurs as a result of the ionization of atoms on essential molecules produced by an immediate interaction with incident radiation

Direct action

The damaging effect, on key molecules, produced by free radicals that are created by the interaction of radiation with water molecules; cell death can result.

Indirect action

Ionization interaction of radiation with water molecules resulting in a separation into oxygen and hydrogen components

Radiolysis

Radiolysis of Water

Ionization of water molecules

Production of free radicals

Production of undesirable chemical reactions and biologic damage

Production of cell-damaging substances

Organic free radical formation

The biologically reactive molecular byproducts formed during radiolysis of water are thought to be what

H + OH

What are the products of the initial interaction when water is irradiated?

HOH

If 2 Hydroxide radicals combine what is produced?

Hydrogen peroxide

If a hydrogen radical and O2 come what’s created?

Hydroperoxide radical

Most biological damages are not cause by radiation instead they are caused by what?

Hydrogen peroxide + hydroperoxyl radical

Concept of radiation dam age resulting from discrete and random events. If a critical location on the master molecule is a target receiving multiple hits from ionizing radiation, it may well be inactivated. Normal cell function will then cease, and the cell will die. If, on the other hand, it receives only a single hit, then the master molecule most likely will still be operational. Useful for explaining cell death and non fatal cell abnormalities caused by expo sure to radiation

Target Theory

The key or master is what

DNA