1Intro to Radiation Biologyis 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

2Radiation reacts with main cellular component: Water

• 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

3Radiation 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

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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?

5Tissues 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

6Clinical effect of acute exposure

Syndrome Symptoms Dose (rad)

Non-clinical worry < 100 rad

Radiation sickness

Nausea, vomiting > 100 rad

HematopoieticSignificant disruption of ability to

produce blood products)> 250 rad

LD50/60d Death in half the population > 250 - 450

rad 

GIFailure of GI tract lining, loss of

fluids, infections> 500 rad 

CNS Brain death > 2,000 rad 

100 rad = 1 Svhttp://www.e-radiography.net/radsafety/rad_biology.htm

7Clinical-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 NONE 0-80%

100 rad = 1 Sv

8Clinical -3

6-10 Sv 10-50 Sv >50 Sv

Delay time 1 hr 30 min 30 min

Therapy Marrow transplant?

Maintain electrolytes

sedatives

Incidence of death

80-90% 90-100% 90-100%

9Nuclear Accident in Japan

• 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.

10continued

• 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.

11Effects 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

12Shallow vs. Deep Dose

• 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.

13Other Acute effects

• 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.

14STRPs: 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.

15STRPs

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.

16Chronic 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?

17Threshold vs. LNT

www.aboutnuclear.org/i/radiation/lnt.jpg

18Hormesis: might a little radiation be good for you?

Small doses consistent with background levels of radiation seem to have a positive effect.

www.giriweb.com/luckey.htm

19Hormesis vs. LNT

• 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.

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21Hypothesis needs a mechanism

• 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