Intro to Radiation Biology
1
is it gonna git you?
• Radiation exposure
– Alpha up to 7.5 MeV
• Stopped in dead layer of normal skin
– Beta: penetrate 4 m thru air per MeV of energy
• Penetrate 0.5 cm in soft tissue per MeV of energy
• Up to 70 KeV: stopped in dead layer of skin
– Gamma, X-ray: high penetrating ability
• Ingestion, inhalation of radioactive material
– Opportunity for continuous radiation
Radiation reacts with main cellular
component: Water
2
• Water comprises 60% of humans, average
• Ionization of water leads to free radical
formation: H* and *OH (where * is unpaired electron)
• Possible reactions
– H* + *OH = HOH (reunite to form water)
– H* + H* = H2;
*OH + *OH = H2O2
• *OH and peroxide are very reactive
– Damage cell membranes, proteins, and DNA
– Possibility of antioxidants as treatment
Radiation damage is at the level of the cell
• Organisms die because organ systems fail
because cells die
Approx. Sv
Cellular effect
0.35 – 1.0
Evidence in chromosomes
> 1.0
1 aberrant chromosome/cell
5-10
Breakdown of lysozomes, autolysis
20-30
Mitochondrial breakdown
30-50
Plasma membrane breakdown
3
4
Cells are not equally sensitive
• 1906 Bergonie and Tribondeau realized that
cells were most sensitive to radiation when
they are:
– Rapidly dividing
– Undifferentiated
– Have a long mitotic future
• The more often they divide, the more chances
for DNA damage to result in cell death.
• Much known about effect on plants
– Couldn’t run away?
Tissues vary in Radiation Sensitivity
Lymphocytes
Connective tissue
Granulocytes
Connective tissue
Endothelial cells, skin
Epithelial tissue
Bone cells
Connective tissue
Nerve cells
Nervous tissue
Brain cells
Nervous tissue
Muscle cells
Muscle tissue
5
6
Clinical effect of acute exposure
Syndrome
Symptoms
Dose (rad)
Non-clinical
worry
< 100 rad
Radiation
sickness
Nausea, vomiting
> 100 rad
Hematopoietic
Significant disruption of ability to
produce blood products)
> 250 rad
LD50/60d
Death in half the population
> 250 - 450
rad
GI
Failure of GI tract lining, loss of
fluids, infections
> 500 rad
CNS
Brain death
> 2,000 rad
http://www.e-radiography.net/radsafety/rad_biology.htm
100 rad = 1 Sv
7
Clinical-2
0-1 Sv
1-2 Sv
2-6 Sv
Delay time
NA
3 hr
2 hr
Therapy
reassurance Blood
monitoring
Transfusion,
antibiotics
Incidence
of death
NONE
0-80%
NONE
100 rad = 1 Sv
8
Clinical -3
6-10 Sv
10-50 Sv
>50 Sv
Delay time 1 hr
30 min
30 min
Therapy
Marrow
transplant?
Maintain
sedatives
electrolytes
Incidence
of death
80-90%
90-100%
90-100%
Nuclear Accident in Japan
9
• SEPTEMBER 30, 1999
• Two of the three workers exposed to radiation
– are in extremely critical condition.
– The number of leukocytes (granulocytes) of the three rose
by two to four times the normal level.
– The % of lymphocytes among white blood cells, which
averages 40 percent among ordinary people also dropped
below 10 percent and the figure for Ouchi and Shinohara is
as low as 2 percent.
– The radiation dose for the two in critical condition estimated
at 8 to 10 sieverts judging from their lymphocytes and overall
condition. When JCO workers remained alive, and one of
the two more exposed improved, the initial estimates were
questioned.
continued
10
• Experts said dose estimates in Sieverts (rems) are
inappropriate for the Tokai workers, since Sieverts
express dose equivalents. Grays, which express
absorbed dose, are used to measure high doses that
produce immediate effects. Experts at France's
Institute of Protection and Nuclear Safety (IPSN) said
the top dose was probably closer to 6 Grays.
• Hisashi Ouchi, 35, died of multiple organ failure at
11:21 PM. Ouchi, whose death came 83 days after the
accident, has become the first person in Japan to die
from radiation exposure at a nuclear-related facility.
Effects on different organ systems
• Blood
– RBCs fairly resistant. Why?
– WBCs very sensitive; bone marrow cells too
• Failure of immune system, clotting
• Digestive system
– Small intestine most sensitive, needs continual
replacement, necessary for nutrient absorption
– Both intestines: blood vessels near surface
• Reproductive: sperm tough, germ line not
– 3-6 Sv cause permanent sterility
11
Shallow vs. Deep Dose
12
• Given equal amount of energy, beta more likely
to cause erythema (red inflammation of skin)
– All energy is deposited there
• Gamma: deep dose
– Low impact on skin, but dose is deeper and more
spread out.
• In a criticality accident like in Japan, both
neutrons and gamma rays, complex effects.
Other Acute effects
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• Effect of acute dose
– Premature aging
– Cancers such as leukemia
• Leukemia most common radiation-induced
cancer
– Increase in change in STRPs
• Simple tandem repeat polymorphisms, “markers”
present in DNA, generally non-coding.
• Acute exposure at Chernobyl of 0.185 Sv
produced 2x background mutation rate.
STRPs: Microsatellite DNA
• Simple Tandem Repeat Polymorphisms
– These are RFLPs because they are defined by or
visible following restriction enzyme cuts.
• Restriction Fragment Length Polymorphisms
– 2-9 nucleotides repeated, shorter than VNTRs
– Small enough number for PCR amplification
– Also called STRs, SSLPs, etc.
– Radiation damage at restriction site changes
fragment length, changes PCR product.
14
STRPs
Primers for both sides of repeated region allow PCR
amplification of DNA; generates PCR products that
differ in length depending on number of repeats.
Becoming the standard method for DNA testing in
forensics labs. Cheaper, easier, more sensitive.
15
Chronic effects
• Long term exposure to low levels of radiation
– No one knows, can’t be statistically demonstrated
– Linear No Threshold hypothesis (LNT) predicts no
safe level of radiation exposure
• Highly controversial
• Forms basis of radiation regulations
– Single exposure of 1 Sv may show clinical effect,
but why would 10 exposures of 0.1 Sv each have
any effect?
16
Threshold vs. LNT
www.aboutnuclear.org/i/radiation/lnt.jpg
17
Hormesis:
might a little radiation be good for you?
18
Small doses
consistent
with
background
levels of
radiation
seem to have
a positive
effect.
www.giriweb.com/luckey.htm
Hormesis vs. LNT
19
• B. Cohen’s test of the LNT hypothesis
– If increased exposure to radiation at any level is
harmful, then living in an area in which radon is
higher should result in greater incidence of cancer.
– Cohen does NOT intend to demonstrate hormesis,
but merely test the LNT hypothesis.
– Hormesis advocates, however, use his data.
20
Hypothesis needs a mechanism
21
• Idea of “dangerous in large amounts, helpful in
small amounts” is awfully “new-age.”
• Stress proteins:
– Apply stress, cells compensate. Heat shock
proteins, up-regulation of chaperonins.
– More active supply of DNA repair proteins
– Stimulation of immune system.
• For more info:
http://www.giriweb.com/luckey.htm