Hypoxic (or anoxic) cells sustain less radiation damage to their DNA than do cells in a well oxygenated environment. The cell-killing effects of ionizing radiation also tend to decrease as the oxygen level decreases.  Or conversely, cell survival increases as the oxygen level decreases. Several studies suggest that oxygen effects at the DNA damage and cell-killing levels can be modeled by multiplying the initial yield of DNA damage by a dimensionless scale factor termed the oxygen enhancement ratio (OER).  Several unpublished studies (Carlson et al.) suggest that the OER is between about 2.8 and 3.2 and is nearly cell type independent.
 

1. Paste the contents of RMR sample file #1 into a new ASCII input file called oer.inp.
2. Open the oef.inp file and append the keyword OER=1 to the end of the line that begins IRAD:
3. Run the RMR simulation for values of the OER from 1 to 4 (increments of 0.5).
4. Create a plot showing the surviving fraction (y-axis, linear scale) vs. OER (x-axis, linear scale).
5. Create a plot showing the LQ radiosensitivity parameter a (y-axis, linear scale) vs. OER (x-axis, linear scale).
6. Create a plot showing the LQ radiosensitivity parameter a/b (y-axis, linear scale) vs. OER (x-axis, linear scale).

• Does the surviving fraction increase, decrease or stay the same as OER increases?
• Does a and a/b increase, decrease or stay the same as OER increases?
• Explain the observed trends in the surviving fraction, a and a/b in terms of first- and second-order repair processes.  Hint: How are the a and a/b parameters related to the initial yield of DNA damage?
• Compare the radiosensitivity of a cell with an OEF of 1 (well oxygenated) to a cell with an OEF of 3 (hypoxic).  Do oxygen effects produce a significant change in the surviving fraction after a 2 Gy dose of radiation delivered at 30 Gy/h (i.e., a typical radiotherapy treatment fraction)?

1. Repeat exercise 1 with the LPL sample file 1.

• Are the trend in  a and a/b the same as those predicted by the RMR?