4. Potentially lethal damage repair
• Under ordinary circumstances, cell death occurs.
• Manipulation of the post irradiation environment increases
survival.
• Cell survival is enhanced if cells are allowed to remain in the density-
inhibited stationary phase of 6 to 12 hours after irradiation.
5. X-ray survival curve for
density inhibited stationary
cells either immediately or 6
to 12 hours after irradiation
6. If several hours were allowed to lapse after
irradiation of the tumour cell, survival was enhanced
7. Cause of PLD repair
• If post irradiation conditions are sub optimal for growth
• No mitosis occurs with damaged chromosomes
• Giving the cell enough time to repair DNA damage
8. Importance of PLD repair
• Radioresistance of tumours is linked to their ability to repair PLD
• Radiosensitive tumours repair PLD inefficiently, but radioresistant
tumours have efficient mechanisms to repair PLD.
• But this hypothesis has never been proven.
9. Sublethal damage
• Under normal circumstances can be repaired in hours.
• If additional SLD (from a second dose of radiation) is added it
interacts to form lethal damage.
10. Sublethal damage repair
• Increase in cell survival is observed, If a given radiation dose is split
into two fractions separated by a time interval.
12. • If an asynchronous population of cells is exposed to a large dose of radiation,
more cells are killed in the sensitive than in the resistant phases of the cell
cycle.
13. 4 R’s of radiobiology
• Repair
• Reassortment: Progression of cells through the cell cycle during
interval between split doses
• Repopulation: increase in surviving fraction, If the interval between split
dose is 10 to 12 hours (This exceeds the length of cell cycle).
• Reoxygenation: the phenomenon, by which hypoxic cells become
oxygenated after a dose of radiation.
14. • Graph A: there is more repair and
small one-day tumours than in large
hypoxic, six day tumours.
• Repair is an active process requiring
oxygen and nutrients
• Graph B: the total x-ray dose
required to result in one surviving
epithelial cells per square millimetre
plotted against time interval between
the two doses
Pattern of SLD repair
15. • More cell survive, if doses split
in 2 fractions
• Because shoulder of the curve
is repeated with each fraction.
• Shoulder of the curve,
manifests the accumulation and
repair of SLD
Factors involved in repair of SLD
16. • Recovery factor: ratio of
surviving fraction for a given
dose delivered as two fractions
compared with single exposure.
• SLD repair is significant for x-
rays, but is almost non-existent
for neutrons
Repair and radiation quality
17. • Dose rate effect results from the
repair of SLD that occurs during
a long radiation exposure.
• Curve F shows the overall
survival curve
• This curve has no shoulder
because low dose rate (LDR)
radiation may be considered to
be an infinite number of infinitely
small fractions.
Dose rate effect
18. Examples of the dose rate effect in vitro and in vivo
• As the dose rate is reduced, the survival curve becomes shallower
and shoulder tends to disappear.
19. • HeLa cells Survival curve has
small initial shoulder (modest
dose rate effect)
• Chinese hamster cells have a
broad shoulder corresponding
to large dose rate effect.
• Because in hamster cells,
apoptotic death is rarely seen.
Dose response curve for Chinese hamster cells
20. • At LDR, the survival curves fan
out.
• There is a greater variation in
slope, because of the variation
in radiosensitivity and repair
times of SLD
• Some cells repair SLD rapidly
and slowly
21. • As the dose rate is lowered
further, cell division begins to
dominate the picture because the
exposure time is longer than the
cell cycle.
• At 0.54 cGy per minute, there is
less survival even for large doses
• Because of cellular proliferation.
Response of mouse jejunal crypt
cells irradiated with gamma rays
22. • Decreasing the dose rate results
in increased cell killing
• Because at about 0.37 Gy per
hour, cell become arrested in G2
(radiosensitive phase)
• At higher dose rates, they are
frozen in the phase of the cycle,
they are in at the start of the
radiation
• At lower dose rates, they
continue to cycle
Inverse dose rate effect
