Basic Biologic Interactions of Radiation

Radiation Biology ME 397P Spring, 2000

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...
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...

Radiation interaction is nonselective Radiation doesnt seek certain cells, etc.

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...
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:
Begin at subcellular level Depend upon where initial interactions* occur * Initial interactions may be caused by excitation or ionization of medium or target

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

Direct 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 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 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 Water
HOH --> HOH+ + e HOH+ --> H+ + OH. OH. + OH . = H2O2
Hydrogen peroxide is very toxic!

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 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

LET
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

RBE
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 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 Damage
Much of damage may be repairable Different kinds of damage (base damage, single-strand breaks, doublestrand breaks, and crosslinking)

Radiation 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.

Actual breaks Stickiness or clumping of chromosomes

Chromosome 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 Aberration

Accident Dosimetry

Radiation Mutation Effects Summary

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 Organelles

Nucleus most important Cell membrane permeability changes Any membrane-bound organelle susceptible to radiation-induced changes

Membrane Leakage

Glossary
Please refer to definitions in glossary of textbook

Coming Attractions...
Bean lab results next week Will be starting Drosophila lab Research paper assigned Exam #1 coming up