1. Fourth lecture

2. The Effects of Radiation on the Cell at the Molecular Level
When radiation interacts with target atoms, energy is deposited, resulting in ionization or excitation.
The absorption of energy from ionizing radiation produces damage to molecules by direct and indirect actions.
For direct action, damage occurs as a result of ionization of atoms on key molecules in the biologic system. This causes inactivation or functional alteration of the molecule.
Indirect action involves the production of reactive free radicals whose toxic damage on the key molecule results in a biologic effect. 2

3. Radiation cellular damage
Direct
Indirect
Neutron
Alpha
X- & gamma rays
Macromolecules
biomembranes
H2O
Damaged molecules
Free radicals
Cell death
Superoxides
Peroxides O2

4. Direct Effects
Direct ionization of atoms in molecules is a result of absorption of energy.
Ionization occurs at all radiation qualities but is the predominant cause of damage in reactions involving high LET radiations such as neutron & alpha.
Absorption of sufficient energy to remove an electron can result in bond breaks.

5. Indirect Actions These effects are mediated by free radicals.
A free radical is an electrically neutral atom
with an unshared electron in the orbital
position.
The radical is electrophilic and highly reactive.
Since the predominant molecule in biological systems is water, it is usually the intermediary of the radical formation and propagation 4

6. Radiolysis of water and free
radicals formation
Free radicals
Molecules
.OH
H2O2 H. H2
HO.2
O.-2

7. Free radicals readily recombine to electronic
Indirect Action
Free radicals readily recombine to electronic
and orbital neutrality. However, when many
exist, as in high radiation, orbital neutrality
can be achieved by:
1.Hydrogen radical dimerization (H2)
2.The formation of toxic hydrogen peroxide (H2O2).
3.The radical can also be transferred to an organic molecule in the cell. 5

8. Indirect Action H· + OH· →HOH (recombination) H· + H· → H2 (dimer)
OH· + OH· → H2O2 (peroxide dimer)
OH· + RH → R· + HOH (Radical transfer)
The presence of dissolved oxygen can modify the reaction by enabling the creation of other free radical species with greater stability and lifetimes
H· +O2 → HO2· (hydroperoxy free radical)
R· +O2 → RO2· (organic peroxy free radical) 6

9. Indirect Action
The transfer of the free radical to a biologic molecule can be sufficiently damaging to cause bond breakage & inactivation of key functions.
The organic peroxy free radical can transfer the radical form molecule to molecule causing damage at each encounter.
Thus a cumulative effect can occur, greater than a single ionization or broken bond. 8