Radiation Biology: Ch 7 pages 111-126

what is radiation biology

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

ionizing radiation chain of reaction

• involves disruption of molecular bonds

• alternations in biochemical pathways

• transformation of a cell

• observable effects at the tissue or whole-body level

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

charge, mass, energy

three determinants of radiation transfer

linear energy transfer (LET,) relative biologic effectiveness (RBE), oxygen enhancement ratio (OER)

radiation loses its energy along its track through a medium, the average energy deposited per unit length of track measured in kev/micron

Linear Energy Transfer

( low or high ) LET has short wavelength high energy waves

Low LET

types of low LET radiation

x-rays, gamma rays, electrons

LET that causes damage primarily by indirect action, does not give up all its energy quickly

low LET

(high or low) LET has mass and charge, lose their energy rapidly over a shorter length of time

high LET

LET that produces more ionizations per unit length of travel and exhaust their energy in a shorter path length

high LET

when is high LET at the greatest risk

when internal contamination occurs

-implanted, ingested, injected, inhaled

describes the relative capabilities of radiations with differing LET’s to produce a particular biologic reaction

relative biologic effectiveness

____ values are similar to values of RBE

WR

LET and RBE are a _____ relationship

direct

Bushong:

when a dose is delivered continuously but at lower dose rate, it is protracted, when radiation is delivered at the same dose in equal portions at regular intervals occurs, its fractionation

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

the oxygen effect

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

oxygen enhancement ratio

increased oxygen = _____ biologic damage

more biological damage

without oxygen damage produced by indirect action may be repaired, but when damage occurs through oxygen mediated process, the end result is permanent

oxygen fixation hypothesis

where does any visible radiation induced injuries always originate

damage at the molecular level

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

molecular damage

what happens when radiation damages a germ cell

damage may be passed on to future generations in the form of genetic mutations

two classifications of radiation interactions

direct or indirect

occurs when ionizing radiation interacts directly with vital biologic macromolecules such as DNA, RNA, proteins, and enzymes

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

direct

this is a multistage process that involves the productions of free radicals that are created by interaction of radiation with water

indirect

direct actions are associated with ____ LET and ____ particles

high LET, and alpha particles

indirect action is associated with ____ LET and _____ particles

low LET, and x-ray/gamma ray particles

the dissociation of water molecules into other products caused by the interaction of radiation with water

radiolysis of water

process of radiolysis

• water molecule struck by radiation and dissociates into 2 ions

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

• ions are unstable

what can happen when water molecule is struck by radiation and breaks into 2 ions (radiolysis)

• positive water and electron recombine

• electron joins with water molecule creating negative water molecule

• positive and negative water molecules are unstable and will break apart

free radical formation

the positive water molecule breaks apart to form hydrogen ion and hydroxyl radical HOH+ → H+ → OH*

the negative water molecule breaks apart to form hydroxyl ion and hydrogen radical HOH- → OH- →H*

end products of radiolysis

formation of an ion pair: hydrogen ion and hydroxyl ion: H+ and OH-

two free radicals: hydrogen radical and hydroxyl radical: H* and OH*

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

what happens if there is a production of undesirable reactions

presence of hydroxyl and hydrogen free radicals is not insignificant

what is a free radical

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

what can free radicals produce

• undesirable chemical reactions and cause biologic damage by transferring their excess energy to other molecules

• their energy can break chemical bonds in other molecules or can form toxic bonds

free radical characteristics

• do not occur normally in nature

• can travel through cell membrane and cause damage in areas away from their origin

• unstable lifetime, less than one millisecond

which radical is most often believed to be the cause of approximately 2/3 of all radiation induced damage

hydroxyl radical (OH*)

what forms hydrogen peroxide

hydroxyl radical bonded with another hydroxyl radical

OH* + OH* → H2O2

what forms a hydroperoxyl formation

hydrogen free radical can combine with molecular oxygen to form a hydroperoxyl radical

H+ + O2 → HO*2

when does indirect action occur

radiation is not immediate cause of injury to the macromolecule and occurs when free radicals produced by radiolysis act on vital molecules such as DNA

energy transfer can rupture one of the chemical bonds, possibly severing one of the side rails or strands of the ladder, called a point lesion

strand breaks

point lesions occur at the side of the radiation strike, repair enzymes are often capable of reversing this damage

single strand breaks

one or more breaks in the sugar phosphate chains, not repaired as easily

double strand breaks

which break is more common with low LET

single strand breaks

which break is more common with high LET

double strand breaks

what happens when the DNA is cut into 2 pieces on a double strand break

the chromosome is itself broken

results in cleaved or broken chromosome, each part has an unequal amount of genetic material and each daughter cell will have the wrong genetic information

double strand break

mutation:

changes in genes caused by the loss or change of a nitrogenous base on the DNA chain, may not be reversible and may generate acute consequences for the cell

when break occurs the ends become sticky and has the ability to adhere to another segment, crossing between structures in many different patterns

covalent cross linking

effects of ionizing radiation on chromosomes

after breakage of chromosome, 2 or more splinters are produced having broken ends that are very chemically active and adhere to another similar end

can rejoin original configuration, create an aberration, or can join other broken ends and create new chromosomes

two types of chromosomal anomalies

chromosomes aberrations or chromatid aberrations

occurs when irradiation occurs early in interphase, before DNA synthesis takes place

chromosome aberration

occur if irradiated later in interphase, after DNA synthesis

chromatid aberrations

breaks rejoin in their original configuration with no visible damage

restitution

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

deletion

a grossly misshapen chromosome may be produced, ring chromosomes, dicentric chromosome, or anaphase bridges. results in cell mutation

broken and rearrangement

chromatids genetic material is rearranged even though the chromosome appears normal

broken and rearrangement without visible damages