Adaptive Response to Low Dose Radiation

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Adaptive Response to Low Dose Radiation
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Adaptive Response

• When large radiation exposure is preceded by a
  small tickle dose, the effect of the large dose
  is sometimes diminished

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• The first time you go to the beach in the
• summer, you dont usually spend eight hoursin
  the sun (UV radiation). You begin by being out
  an hour or
• two and add additional time as your skin
• adapts to the sunny condition and develops
• protective mechanisms.

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Adaptive Response

• In some cases, cells also show an adaptive
  response to ionizing radiation, although
  researchers are still trying to understand how
  the protective mechanisms work. Small doses of
  radiation appear to stimulate protective
  responses, triggering DNA repair mechanisms and
  the elimination of severely damaged cells.

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Adaptive response has been demonstrated on
various levels

• Molecular
• Cellular
• Tissue
• Whole animal
• Human

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and for a variety of biological changes

• Chromosome damage (Olivieri 1984)
• DNA damage (Le et al. 1998)
• Mutation (Sommers et al. 2004)
• Cell transformation (Redpath and Antoniono 1998)
• Cell killing (Ishi and Watanabe 1996)
• Gene Induction (Yin 2003)
• Animal survival (Mitchel et al. 1986)

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Adaptive response is specific
There is a genetic basis for adaptive response.
It has been demonstrated in cell lines, tissues,
animal lines and individuals. It is demonstrated
for some biological endpoints. More symptoms and
endpoints need to be studied.
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Adaptive response
90
80
70
60
Aberrations
50
Observed
40
Expected
30
20
10
0
0
0.5
150
0.5 150
Dose cGy
Shadley and Wolff 1987
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Adaptive response

• What about CANCER?

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Cells transforming to cancerous cells
Sometimes a low radiation exposure of 1- 10 cGy,
close to the yearly background level, appears to
act as the tickle dose, and reduces cancer
rates.
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Adaptive responses for leukemia
Mice that were exposed to a small tickle dose
of radiation before the large dose of radiation,
developed cancer later and lived longer than the
mice that received only a large dose of radiation.
1.0
In this experiment, mice that were exposed to
high doses of radiation died of leukemia before
600 days.
0.8
0.6
Survival Probability
0.4
0.2
0.0
About half of a population of mice are expected
to die by the time they are 700 days old, and
usually all die before 1,000 days.
0 200 400 600 800
1000
Time (days)
Mitchel et al 1999
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Lymphoma in mice
Although the survival rate was not affected by 1
or 10 cGy radiation exposures, the control
group, which did not receive any radiation,
developed more tumours than either of the
radiated groups.
50 40 30 20 10 0
0 cGy 1 cGy 10 cGy
Number of Tumours
0 20 40 60
80 100
Death
Mitchel et al. 2003
Lymphomas in Trp53/- Mice
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Bone tumours in mice
There were also fewer bone tumours when the mice
were given 1 cGy of radiation than when they had
no radiation. However, this time, mice receiving
10 cGy developed more tumours than the controls
before they died.
25 20 15 10 5 0
0 cGy 1 cGy 10 cGy
Number of Tumours
0 20 40 60
80 100
Death
Osteosarcomas in Trp53/- Mice
Mitchel et al. 2003
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Relative risk for different types of
radiation-induced human cancer
5 4 3 2 1 0
Relative Risk
Normal risk without radiation
0.1 1
10 100
Dose (cSv)
Redpath et al.2001
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Impact of adaptive response

• Adaptive response may be useful in radiation
  therapy to protect normal tissue.
• Induction of repair genes may decrease the
  detrimental effects of radiation.
• Because adaptive response is demonstrated at low
  doses and dose-rates, it may someday have an
  impact on radiation protection standards and
  regulations.