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MOLECULAR AND CELLULAR RADBIO EASY GUIDE

Radiation Interaction with Water
• The principal radiation interaction in the body
In Vitro
• Irradiation outside of the cell or body
In Vivo
• Irradiation with the cell or body
IRRADIATION OF MACROMOLECULES
Solution
• A liquid that contains dissolved substances
Three Major Effects When Macromolecules Are Irradiation in a Solution In Vitro
• Main-chain Scission, Cross-linking & Point Lesion
Main-Chain Scission
• The breakage of the backbone of the ling-chain macromolecules
• Result:
o Reduction of a long, single molecule into many smaller molecules
• Effects:
o Reduces the size of the macromolecules
o Reduces the viscosity of the solution
▪ Very thick & slow to flow
• Measurement of Viscosity: determines the degree of main-chain scission
Cross-Linking
• Process of side spurs created by irradiation & attached to a neighboring
macromolecules or to another segment of the same molecule
• Effect: increases the viscosity of the macromolecular solution
Point Lesion
• Any change that results in the impairment or loss of function at the point of a single
chemical bond
• Not detectable
At low radiation doses, point lesion are
considered to be the cellular radiation
damage that results in the late radiation
effects observed at the whole-body level!

Catabolism
• The reduction of nutrient molecules for energy
Anabolism
• The production of large molecules for form and function
Metabolism consists of catabolism and
anabolism!
Translation
• Process of forming a protein molecule from messenger RNA
Transcription
• Process of constructing mRNA
Proteins
• More abundant than nucleic acids
• Less radiosensitive than nucleic acids
DNA
• The most important molecule in the body
• Not abundant in the cell
DNA is the most radiosensitive molecule!
G1 Portion of Interphase
• Deoxyribose, phosphate & base molecules accumulate in the nucleus
• DNA is in familiar double-helix form
S Portion of Interphase
• The DNA separates like a zipper
• Two daughter DNA molecules are formed
Chromosomes
• Control the growth & development of the cell

Radiation Effects on DNA
• Chromosome aberration or cytogenetic damage
• Abnormal metabolic activity
• Structural change

Type of Chromosome Aberrations
• Terminal deletion
• Dicentric formation
• Ring formation
Unobservable Radiation Response of DNA
• Main-chain scission with only one side rail severed
o Result: structural change
• Main-chain scission with both side rail severed
o Result: structural change
• Main-chain scission & subsequent cross-linking
o Result: structural change
• Rung breakage causing separation of bases
o Result: structural change
• Change in or loss of a base
o A molecular lesion of DNA
o Destroys the triplet code
o May not be reversible
Point Lesion
• A molecular lesion of DNA
• Critical Consequence: the transfer of incorrect genetic code to one of the two
daughter cells
Three Principal Observable Effects
• Cell death
• Malignant disease
o Molecular level
o Linear, nonthreshold dose-response relationship
• Genetic damage
o Molecular level
o Linear, nonthreshold dose-response relationship

Radiolysis of Water
• Dissociation of water into other molecular products as a result of irradiation
• Initial Result
o Ion Pair: HOH+& e• Final Result
o Ion Pair: H+ & OHo Two Free Radicals: H* & OH*
Irradiation of Water
• It represents the principal radiation interaction in the body

Free Radical
• An uncharged molecule that contains a single unpaired electron in the other shell
• Lifetime: < 1 ms
Hydrogen Peroxide
• Poisonous to the cell & therefore acts as a toxic agent
• Chemical Formula: H2O2
• Formed By:
o HO* + HO* or
o HO*2 + HO*2
Hydroperoxyl Radical
• The principal damaging product after radiolysis of water along with Hydrogen
peroxide
• Chemical Formula: HO*2
• Formed By: H* + O2
Organic Molecules
• Symbol: RH
Organical Free Radicals
• H* & R*
o Formed By: RH + irradiation
• RO*2
o Formed By: R* + O2
DIRECT & INDIRECT EFFECTS
Direct Effect
• If the initial ionizing event occurs on the target molecule
Indirect Effect
• If the initial ionizing event occurs on a distant, noncritical molecule
• The energy is transferred to the target molecule
The principal effect of radiation on humans is indirect!
Target Theory
• For a cell to die after radiation exposure, its target molecule must be inactivated
• It was used to represent cell lethality
• It can be used to describe nonlethal radiation-induced cell abnormalities
DNA is the target molecule!

Target
• An area on the cell occupied by the target molecule or by a sensitive site on the
target molecule
Hit

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•
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Radiation interaction with the target or molecules
It occurs through both direct & indirect effect
It isn’t simply an ionizing event, but rather an ionization that inactivates the target
molecule

Direct & Indirect Effects
• Low-LET Radiation & Absence of Oxygen:
o Low probability of hit on the target molecules
▪ Rationale: relatively large distances between ionizing event
• Low-LET Radiation & Presence of Oxygen:
o High probability of hit on the target molecules
▪ Rationale:
• Formation of free radical
• Enlarged volume of effectiveness surrounding each ionization
• High-LET Radiation & Absence of Oxygen:
o High probability of a hit by direct effect
▪ Rationale: close distance between ionization event
• High-LET Radiation & Presence of Oxygen:
o Does not result in additional hits
▪ Rationale: the maximum number of hits has already been produced
by direct effect with high-LET radiation
CELL SURVIVAL KINETICS
Cell Cloning
• Process by which normal cells produce a visible colony in a short time
The lethal effects of radiation are determined
by observing cell survival, not cell death!
Two Models of Cell Survival
• Single-Target, Single-Hit Model
• Multi-Target, Single-Hit Model
Single-Target, Single-Hit Model
• It applies to biologic targets such as enzymes, viruses & bacteria
• Equation:
o S = N/No = e-D/D37
Radiation interacts randomly with matter!

D37
•

When the radiation dose reaches a level sufficient to kill 63% of the cells (37%
survival)
• A measure of the radiosensitivity of the cell
• Low D37: highly radiosensitive
• High D37: highly radioresistant
Multi-Target, Single-Hit Model
• It applies to more complicated biologic system such as human cells
• Equation:
o S = N/N0 = 1 – (1 - eD/D0)n
• It represents a threshold
Cell Survival
• Very Low Radiation Dose: nearly 100%
• High Radiation Dose: fewer cells survive
o Rationale: more sustain a hit in both target molecules
o Survived Cells: have one target hit
o Dose-Response Relationship: appear as single-target, single-hit model
D0
•
•
•
•
•

The mean lethal dose
A constant related to the radiosensitivity of the cell
It is equal to D37 in the linear portion of the graph
Large D0: radioresistant cells
Small D0: radiosensitive cells

Extrapolation Number
• The target number
DQ
•
•
•
•

The threshold dose
A measure of the width of the shoulder of the multitarget single-hit model
It is related to the capacity of the cell to recover from sublethal damage
Large DQ: the cell can recover readily from sublethal radiation damage

Sublethal Damage
• A damage that must be accumulated before the cell dies
• Wider Shoulder:
o More sublethal damage that can be sustain
o The higher the value of DQ

Split-Dose Irradiation
• Designed to describe the capacity of a cell to recover from sublethal damage

CELL CYCLE EFFECTS
Cell-Cycle Time/Cell Generation Time
• The average time from one mitosis to another
• Human Cells: approximately 24 hrs
• Neurons: hundreds of hrs
o do not normally replicate
• Longer Generation Time
o Results From: lengthening of the G1 phase of the cell cycle
G1 is the most time variable of cell phases!
Age-Response Function
• The pattern of change in radiosensitivity as a function of phase in the cell cycle
• Mitosis:
o The most sensitive
o Lower fraction of surviving cells
• G1-S Transition: the next most sensitive
• Late S-Phase: the most resistant
Human cells are most radiosensitive in M & most resistant in late S!
LET, RBE & OER
Linear Energy Transfer (LET)
• At Very High LET: cell survival kinetics follows the single-target, single-hit model
o Examples: alpha particles & neutrons
• At Low LET: cell survival kinetics follows the multi-target, single-hit model
o Example: x-rays
• Mean Lethal Dose: greater after low-LET irradiation than after high-LET
irradiation
Relative Biologic Effectiveness (RBE)
• Formula:
RBE =

D0 (x-radiation) to produce an effect
D0 (test radiation) to produce the same effect

Oxygen
• The most completely studied dose modifier
• Presence of Oxygen: maximizes the effect of low-LET radiation

•

Anoxic Cells: requires higher dose to produce a given effect

Oxygen Enhancement Ratio
• Designed to measure the magnitude of the oxygen effect
• Formula:
OER =

D0 (anoxic) to produce an effect
D0 (oxygenated) to produce the same effect

LET determines the magnitude of RBE & OER!



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