Basic Biologic Interactions of Basic Biologic Interactions of RadiationRadiation

Radiation Biology

ME 397P

Spring, 2000

Keep in Mind...Keep in Mind...

• All radiation interactions are probability functions

• We can predict overall effects, but cannot predict specific events: which cell or DNA molecule will be affected

Keep in Mind...Keep in Mind...

• Time frame

• Energy is transferred from photon/particle very quickly (10-17 to 10-15 seconds)

• Chain of events may appear to be simultaneous

Keep in Mind...Keep in Mind...

• Radiation interaction is nonselective

• Radiation doesn’t seek certain cells, etc.

Keep in Mind...Keep in Mind...

• Radiation damage to the cell cannot be distinguished from damage caused by other sources such as chemicals, heat, or trauma

• This concept makes it difficult to tell what caused damage - especially when studying effects of low-level radiation

Keep in Mind...Keep in Mind...

• Radiation effects exhibit a latent period during which no evidence of damage is present

• Latent period may last from few minutes to decades (length is dependent on dose and type of cells involved)

Initial Changes:Initial Changes:

• Begin at subcellular level

• Depend upon where initial interactions* occur

• * Initial interactions may be caused by excitation or ionization of medium or target

TargetTarget

Usually a critical biologic macromolecule (e.g., DNA)

Direct Interaction of RadiationDirect Interaction of Radiation

• Energy of radiation is deposited directly in critical target resulting in excitation or ionization. Starts a chain reaction which may or may not be fatal to cell (e.g., may be repaired)

• More likely to occur with high-LET radiation such as particles or neutrons

Indirect Interaction of RadiationIndirect Interaction of Radiation

• Involves the radiolysis of water

• Is the most common effect since cell is primarily water

• Example: For every one DNA molecule, there are 1.2X107 water molecules

Radiolysis of WaterRadiolysis of Water

• Involves the production of a free radical (highly reactive species)

• Free radicals are designated by a dot and contain a single unpaired electron in outer electron shell

Radiolysis of WaterRadiolysis of Water

HOH --> HOH+ + e

HOH+ --> H+ + OH.

OH. + OH . = H2O2

Hydrogen peroxide is very toxic!

Direct or Indirect Effect?Direct or Indirect Effect?

Experiments have been performed with simple organisms such as Artemia (brine shrimp) cysts in wet and dry conditions. Which tolerated the

larger dose? Can you think of other ways researchers could study these effects?

LET and RBELET and RBE

• LET (Linear Energy Transfer) - rate at which energy of radiation is transferred to medium in units of keV/micron

• RBE (Relative Biological Effectiveness) - comparison of dose of test radiation to dose of 250 keV x-rays to produce same biological effect

LETLET

• X-rays and gamma rays are low-LET radiations

• Alpha and fast neutrons are high-LET radiations

• LET directly related to ionization and therefore, biological damage

RBERBE

• High-LET results in high RBE

• Is similar to Quality Factor (Q)

• RBE = dose of 250-keV x-ray to produce same effect divided by dose of test radiation to produce same effect

• Same biological endpoint (effect) is constant; not doses

Radiation and Cellular TargetsRadiation and Cellular Targets

• Damage to a critical molecule which results in significant impact on cell

• Radiation does not seek out targets

• Most critical site in cell is probably DNA in nucleus

DNA DamageDNA Damage

• Much of damage may be repairable

• Different kinds of damage (base damage, single-strand breaks, double-strand breaks, and crosslinking)

Radiation Effects on ChromosomesRadiation Effects on Chromosomes

• DNA damage may not be visible as chromosome damage

• Can have actual visible changes in chromosomes

• Chromosome damage can occur in either sex cells or somatic cells

Structural Changes in Chrom.Structural Changes in Chrom.

• Actual breaks

• “Stickiness” or clumping of chromosomes

Chromosome DamageChromosome Damage

• Broken pieces may correctly rejoin

• Piece is “lost” (acentric fragment)

• Rearrangement of broken ends yield rings, dicentrics, etc.

• Rearrangements not visible, but genetic material has been affected resulting in a mutation

Ring Chromosome AberrationRing Chromosome Aberration

Accident Accident DosimetryDosimetry

Radiation Mutation Effects Radiation Mutation Effects SummarySummary

• Germ cell changes may produce genetic effects (future generations). Somatic effects will cause changes in exposed person only.

• Radiation effects are nonspecific (no radiounique effects)

• Most mutations are undesirable

Radiation Effects on Other Radiation Effects on Other OrganellesOrganelles

• Nucleus most important

• Cell membrane permeability changes

• Any membrane-bound organelle susceptible to radiation-induced changes

Membrane LeakageMembrane Leakage

GlossaryGlossary

Please refer to definitions in glossary of textbook

Coming Attractions...Coming Attractions...

• Bean lab results next week

• Will be starting Drosophila lab

• Research paper assigned

• Exam #1 coming up