4 R of radiobiology

1. 1st year Resident
DR.Asmita Rayamajhi

3.  Four R’s of radiobiology explains the rationale
behind the fractionation of radiotherapy.
 REPAIR
 REASSORTMENT
 REPOPULATION
 REOXYGENATION

5.  Single strand break
 Double strand break

7.  LETHAL DAMAGE:irreversible,irreparable and
leads to cell death.
 POTENTIALLY LETHAL DAMAGE:
Radiation damage that can be modified by
postirradiation environmental conditions.
 SUBLETHAL DAMAGE:Repaired in hours unless
additional sublethal damage is addded.

8.  If cells are prevented from dividing by creating
suboptimal growth condition for 6 hrs after
irradiation,damage can be repair
 Invitro:by keeping cells in saline

9.  Operatinal term for increase in cell survival if
given radiation dose in split into two fractions
separated by time interval

10.  Base Excision Repair(BER)
 Nucleotide Excision Repair(NER)
 DNA Double–strand Break Repair
 Nonhomologous End joining
 Homologous Recombination Repair
 Others
 Single strand annealing
 Cross link repair
 Mismatch Repair

11.  Single base mutation that is first removed by a
glycosylase/DNA lyase
 Removal of the sugar residue by an AP
endonuclease
 Replacement with the correct nucleotide by DNA
polymerase
 Completed by DNA ligase III-XRCC –mediated
ligation

12.  Nucleotide excision repair removes bulky adducts
in the DNA such as pyrimidine dimers.
 The process can be subdivided into pathways
 Global genome repair(GER)
 Transcription coupled repair(TER)

14.  Occurs in late S/G2
phase
 Undamage sister
chromatid
as template
 Error free

15.  Occurs in G1 phase
 No template
 Fast but error prone
 Accounts for
premutagenic lesion in
DNA of human cell by
ionizing radiation

16.  Cells may be in different phases of cell cycle
during irradiation
 Cells in M phase most radiosensitive and S phase
radioresistant
 Cells surviving in first dose of radiation may reach
sensitive phase in second dose
 Sensitization due to reassortment causes
therapeutic gain,

18.  Process of increase in cell division seen in
normal and malignant cells after irradiation
 In normal tissues.
 Acute Responding tissue:stem cells,GI
epithelium,skin,oropharyngeal mucosa
 Late Responding tissue:renal tubular
epithelium,oligodendrocytes,schwann
cells,endothelium

19.  Some tumors exhibit accelerated repopulation,a
marked increase in their growth fraction,doubling
time and decrease in cell cycle time.
 Dangerous phenomenon that is present when
treatment exceeds over 5 weeks.

20.  Tumor less than 1mm are fully oxic
 Over 1 mm develops region of hypoxia.
 Hypoxia in tumor results from
 Acute hypoxia
 Chronic hypoxia

21.  Temporary closing or blockage of particular blood
vessels
 When dose of radiation is delivered,a propotion of
tumor cells become hypoxic,but if radiation is
delayed different grp of cells become hypoxic.

22.  Results from limited diffusion distance of oxygen
in respiring tissues
 Distance oxygen can diffuse in respiring tissue is
about 70 micrometer

24.  Process by which hypoxic cells become
oxygenated after a dose of radiation.
 Tumor contains the mixture of aerated and
hypoxic cells
 Dose of radiation kills greater proportion of
aerated than hypoxic cells
 Radiation if given in series of fractions separated
in time sufficient for reoxygenation to occur,the
presence of hypoxic cell doesnot greatly influence
the response of tumors.

26.  Reoxygenation in tumors have :
 Fast component
• Seen in acute hypoxia
• Occurs within hours
• Temporary closed vessels reopen
 Slow component
• Seen in chronic hypoxia
• Occurs within days
• Tumor shrink in size .surviving cells previously
beyond the range of oxygen diffusion come closer
to blood supply.

27. THANK YOU