Radiation Biology

Question 1

Which phases of the cell cycle are cells must radioresistant and radiosensitive

Answer 1

1. Resistant - late S - more repair by homologous recombinant than non-homologous end joining
2. Sensitive - G2/M - chromatin compaction and poor repair competence

G1 - intermediate - open structure of DNA

Question 2

Explain the graph

Answer 2

Survival curve - decline of survival with increasing dose

Question 3

Direct and Indirect effects of Ionising Radiation on the Human Body

Answer 3

Direct action: a secondary electron interacts with the DNA to produce an effect.
Indirect action: a secondary electron interacts with a water molecule to produce a hydroxyl radical (OH-), which damages the DNA.

Example: In direct action, x-ray photon absorption leads to interaction with DNA.

Question 4

Radiation Lesions in DNA

Answer 4

Radiation causes lesions in DNA such as single and double strand breaks, base damage, protein-DNA crosslinks, and protein-protein crosslinks.
The number of DNA lesions generated by irradiation is large, but the number leading to cell kill is small.

Example: Dsb play a critical role in cell killing.

Question 5

Major types of DNA Repair

Answer 5

Enzymatic mechanisms of DNA repair include non-homologous end joining (NHEJ) and homologous recombination (HR) for double strand breaks.
NHEJ operates throughout the cell cycle and is error-prone. HR requires sequence homology and operates in late S or G2 phases.

Example: NHEJ repair dominates in G1/S-phases.

Question 6

Damage recognition and signalling

Answer 6

Recognition of radiation damage involves ATM binding to DNA termini, activating CHK kinases and p53. This leads to G1 arrest to allow for DNA repair.
Apoptosis can also be initiated by p53 after irradiation in specific cell types.

Example: ATM kinase activity phosphorylates p53.

Question 7

Consequences of unrepaired DNA damage: Chromosome damage

Answer 7

Unrepaired DNA damage can lead to mutations affecting base pairing, coding, transcription, and gene expression. Chromosome analysis methods can detect unrepaired DNA damage.
Aberrant chromosomes like rings, dicentrics, and translocations can arise from broken ends rejoining.

Example: Dicentric chromosomes have two centromeres.

Question 8

Radiobiological definition of cell death

Answer 8

Cells are considered ‘killed’ by radiation if they lose reproductive integrity.

Question 9

What is a dicentric chromosome?

Answer 9

An abnormal chromosome with two centromeres

Centromere - the center of the chromosome where microtubules attach during cell division

Question 10

What are chromosome translocations?

Answer 10

Changes where a chromosome breaks and the pieces attach to other chromosomes

Question 11

How are cells generally regarded as ‘killed’ by radiation?

Answer 11

If they have lost reproductive integrity, not by whether they physically survive in the population.

Question 12

What are the mechanisms that can lead to loss of reproductive integrity in cells due to radiation?

Answer 12

Apoptosis, necrosis, mitotic catastrophe, or induced senescence (deterioration with age)

Question 13

What is apoptosis?

Answer 13

Programmed cell death with a strong feature in embryological development and lymphocyte turnover

Question 14

What is the gold standard for measuring the radiosensitivity of a cell population?

Answer 14

Retention of reproductive integrity or mitotic intactness i.e. the ability of a cell to undergo more than 5-6 cell divisions

Question 15

How is cell survival calculated after irradiation?

Answer 15

By correcting for the ‘plating efficiency’ of unirradiated cells

Question 16

What is the most common model used for survival curves in radiation biology?

Answer 16

The linear-quadratic model, fitted using a second-order polynomial, with the constants α and β describing the decline of survival with increasing dose

Question 17

When do renewing cells in a growing population participate in the cell cycle?

Answer 17

When not resting in Go phase

Question 18

Which cell cycle phase is most radioresistant?

Answer 18

Late S-phase

Question 19

Which cell cycle phase is most radiosensitive?

Answer 19

G2/M

Question 20

What does Relative Biological Effectiveness (RBE) take into consideration?

Answer 20

Both effective and equivalent dose and how they will affect a particular organ system

Question 21

What helps explain radioresistance in G1?

Answer 21

Chromatin compaction

Chromatin compaction and poor repair competence (reduced enzyme access) could explain the high radiosensitivity in G2/M.

Question 22

What is Relative biological effectiveness (RBE)?

Answer 22

Takes into consideration both effective and equivalent dose and how they will affect a particular organ system.

Comparison of effects of different types of radiation is expressed as relative biological effectiveness (RBE).

Question 23

What is RBE defined as?

Answer 23

The ratio of doses of γ rays (Dγ-ray) and the test radiation (Dr) required to produce an equal amount of a particular biological effect.

A dose of 1 Gy of α particle produces a much larger amount of a chosen biological effect than 1 Gy of γ rays.

Question 24

What is the ‘shoulder’ of a survival curve a reflection of?

Answer 24

The repair capacity of a cell population.

The ‘shoulder’ or the curvature of a survival curve is usually considered to be a reflection of the repair capacity of a cell population.

Question 25

What are bystander effects in radiation biology?

Answer 25

Cells close to irradiated cells but not themselves exposed to radiation may exhibit damage similar to that caused by radiation.

Currently the literature on bystander effects remains controversial.

Question 26

What is the oxygen enhancement ratio (OER) used for?

Answer 26

To determine the dose in hypoxia divided by the dose in air to achieve the same survival level.

Sensitization by oxygen has generally been explained by the oxygen fixation hypothesis.

Question 27

What is the dose reduction factor (DRF) of cysteine or cysteamine in whole body irradiated mice?

Answer 27

1.8

In whole body irradiated mice, addition of cysteine or cysteamine is protective with a dose reduction factor (DRF) of 1.8.