Rad 31: Exam #3 (Part 2&3 - Molecular & Cellular Radiobiology)

Human body contains...

80% water molecules.

In vitro

Irradiation outside the body

In vivo

Irradiation within the body

Macromolecules contain...

A very large number of atoms.

Ex: protein or nucleic acid

In vitro, 3 effects can occur:

Main-chain scission

Cross-linking

Point lesion

Main-chain scission

Radiation induced breakage of long-chain macromolecule into many smaller molecules.

Measurements of viscosity shows degree of main-chain scission.

Cross-linking

Process of side spurs created by irradiation and attached to neighboring macromolecules.

Radiation-induced cross-linking increases viscosity.

Point lesion

Radiation induced disruption of a single chemical bond.

At low doses of radiation, point lesion have cellular radiation damage resulting in stochastic effects.

Macromolecule Synthesis

Metabolism consist of catabolism and anabolism.

Synthesis of proteins and nucleic acid critical to survival and reproduction.

Catabolism

Reduction of nutrient molecules for energy.

Anabolism

Production of large molecules for form and function.

Genetic code of DNA

Translation, transferred, and transcription.

Translation

Process of forming a protein molecule from messenger RNA.

Transfered

Addition of an amino acid during translation.

Transcription

Process of constructing mRNA.

Radiation damage to any part of cell

Late stochastic effects or cell death.

DNA

Most important molecule in body since it contains genetic info for each cell.

Most radiosensitive molecule.

Nucleus contains

Complexed DNA to form chromosome.

Chromosomes control

Development and growth of cell.

If the chromosome is damaged, it can lead to cell death.

Deterministic effect

If several cells are involved, that particular tissue/organ can be damaged.

Stochastic effect

Rapid, abnormal metabolic activity causing radiation-induce malignant disease.

Radiation response of DNA

Main-chain scission only side rail severed.

Main-chain scission with both side rails severed.

Main-chain scission and subsequent cross-linking.

Rung breakage causing a separation of bases.

Change in or loss of a base.

3 observable effects from irradiating DNA

Malignant disease

Genetic damage

Cell death

Ionic bonding

Occurs when two atoms are bound together by the attraction of their opposite charges.

Giving up electrons

Covalent bonding

Sharing of electrons.

Radiolysis of water

Separation of water into other molecular products due to irradiation.

Water is irradiated -> ionized = two ions (ion pairs)

Radiolysis of water: 2 process can occur

1. Ion pair may rejoin into a stable water molecule.

2. If ions don't rejoin, the negative ion may rejoin another water molecule.

Final result of radiolysis of water

Is an ion pair and 2 free radical.

Free radical

Uncharged molecule that contains a single unpaired electron in the outer shell.

Free radicals are unstable and disrupt the bonds of cell.

Direct effects

Ionizing event occurring on the target molecule.

Indirect effects

Ionizing event occurring on a distant molecule.

Free radicals with excess energy damage target molecule.

Principle effects of radiation on human is indirect.

Target theory

Theory that a cell will die if target molecules are inactivated by radiation exposure.

DNA is the target molecule.

Hit

When radiation interacts with the cell.

Hits occur in indirect and direct effects.

No oxygen vs oxygen

No oxygen =low LET radiation.

Oxygen =high LET radiation.

Radiation exposure results in 2 types of cell survival

1. Single-target, single-hit model.

2. Multi-target, single-hit model.

Single-target hit model

Model of radiation dose-response relationship for enzymes, viruses, and bacteria.

Once radiation hits the target (bacteria), any other hits don't matter since target already inactivated (killed).

Multi-target, single-hit model

Model of radiation dose-response relationship for more complicated biologic system.

Ex: Human cell with 2 targets, each must be inactivated for cell death.

Low doses of radiation = cell survival 100%. As dose increases, fewer cells survive due to more hits in both target molecules.

High doses of radiation = all cells that survive have one hit on target

Recovery

Cells that recover from dose can continue to repopulate.

More dose = more cell damage.

Cell-Cycle Effects

Is the average time from one mitosis to another.

Normal proliferation of human cells is 24 hours.

Cells in mitosis stage extremely sensitive.

LET (Linear Energy Transfer)

Measure of rate at which energy is transferred from ionizing radiation to tissue.

At high LET radiation = single-target, single-hit model.

At low LET radiation = multi-target, single-hit model.

RBE (Relative Biologic Effectiveness)

With RBE, as LET of radiation increases, the ability to produce biologic damage also increases.

OER (Oxygen Enhancement Ratio)

Tissue more sensitive to radiation when irradiated in an oxygenated state.

Cellular Radiation Effects

Mitotic delay.

Reproductive failure.

Interference of function.