Hall 6 - OER

Question 1

What is OER?

Answer 1

Ratio of doses under hypoxic over aerated conditions (for same biological effect)

Question 2

What is OER for low LET?

Answer 2

2.5-3.5

Question 3

What is OER for high LET?

Answer 3

1-1.6

alpha particles OER = 1 = no OER
neutrons OER = 1.6

Question 4

OER is always > ____

Answer 4

1

Question 5

When DNA radicals are created by free radical intermediates in hypoxic conditions, what happens?

Answer 5

Repair by sulfahydryl group (SH)

Question 6

When DNA radicals are created by free radical intermediates in aerated conditions, what happens?

Answer 6

They react with O2 to form oxygen radicals which “fix” the damage (cannot be repaired)

Since high LET relies less on free radical intermediates (more direct action), lower OER

Question 7

How long is oxygen required to create an aerated environment?

Answer 7

10^-5 seconds (lifespan of the DNA radical)

Must be present prior to irradiation to within a few microseconds after

Question 8

What oxygen concentration is required for radiosensitization?

Answer 8

0.5% (3 mm Hg)
Results in radiosensitivity halfway between full hypoxia and full aeration

Question 9

At what level does radiosensitization by oxygen plateau?

Answer 9

30 mm Hg (pO2 venous blood)

Question 10

What is the hypoxic cell fraction?

Answer 10

= (surviving fraction under normally-oxygenated conditions) / (surviving fraction under full hypoxia)

Question 11

What causes chronic hypoxia?

Answer 11

Limited diffusion distance of oxygen
(150 micrometers at arterial end of a capillary)

Question 12

What causes acute hypoxia?

Answer 12

Transient closing of a tumor blood vessel due to malformed vasculature

Question 13

What is the gold standard for measuring hypoxia in vivo?

Answer 13

Oxygen probes

Can also use chemical markers (labeled 2-nitroimidazoles) or endogenous markers (HIF-1, CA9)

Question 14

What is D0 for most aerated mammal cells?

Answer 14

1-2 Gy

D0 = dose for one lethal event per target

Question 15

What is D0 for most hypoxic mammal cells?

Answer 15

2-6 Gy

Question 16

What are the fast and slow components of reoxygenation?

Answer 16

Fast: acutely hypoxic cells get O2 from transiently closed blood vessels reopening

Slow: chronically hypoxic cells move closer to blood supply as tumor shrinks

*Hypoxic fraction remains relatively stable at successive RT fractions (evidence for reoxygenation)