Hall - Radiobiology

Question 1

Do

Answer 1

dose of radiation that produces lethal event per cell

–>37% of irradiated cells are still viable

Question 2

Do for mammalian cells

Answer 2

1-2 Gray
1 Gy-->
40 DSBs
1000 SSBs
>2000 base damage
30 DNA-DNA crosslinks

Question 3

effect of SSBs on cell survival

Answer 3

little consequence for cell kill d/t easy repair; mutation in mismatch repair–>misrepair–>mutation develops

Question 4

MOST IMPORTANT lesion produced in chromosomes by radiation

Answer 4

double strand breaks (DSBs)

may result in killing, carcinogensis, mutation

Question 5

rate of DSB formation with radiation

Answer 5

produced linearly with dose bc formed by single tracks of ionizing radiation

Question 6

spur

Answer 6

up to 100 eV of electrons; involves 3 ion pairs; with electromagnetic radiation (x-rays or gamma rays), 95% of energy deposition is in the form of spurs

Question 7

cluster lesions

Answer 7

= locally multiply damaged sites = wide variety of complex lesions d/t spurs or blobs having dimensions similar to DNA double helix; ex. a DSB accompanied by base damage and the loss of genetic information

Question 8

blobs

Answer 8

produced moreso with densely ionizing radiation (neutrons or alpha-particles)

Question 9

methods of measuring DNA strand breaks

Answer 9

1. sucrose gradient sedimentation
2. alkaline and neutral filter elution
3. nucleotide sedimentation
4. pulsed-field gel electrophoresis (PFGF) - MOST COMMON for induction and detection of DSBs
5. single-cell gel electrophoresis (comet assay) - high sensitivity and specificity for SSBs, less so for DSBs
6. DNA damage-induced nuclear foci (radiation-induced foci)

Question 10

kinetics of DSB repair after irradiation

Answer 10

two first order components (Fast and slow); rejoining of incorrect DNA ends originates solely from slowly rejoining DSBs and this subset of radiation-induced DSBs is what is manifested as chromosomal damage

Question 11

DNA repair pathways

Answer 11

1. base excision repair
2. nucleotide excision repair
3. mismatch repair
4. nonhomologous end joining (NHEJ)
5. homologous recombination repair (HRR)
6. single-strand annealing (SSA) - uses homology-based mechanism; error-prone
7. alternative DNA end-joining (Alt-EJ) - active in cells where classical NHEJ is lost; error prone
8. crosslink repair