THE BIOLOGICAL EFFECTS OF IONIZING RADIATION

1. THE BIOLOGICAL EFFECTS OF IONIZING RADIATION Lesley Hines lhines@ehs.ufl.edu Environmental Health and Safety Radiation Control and Radiological Services

2. The Effects of Radiation

3. Time Scales • Physics • 10-15 seconds • Initial ionization • Chemistry • 10-9 seconds • Lifetime of free radicals • Biology • Hours (103 seconds) for acute effects • Generations (1010+ seconds) for genetic mutations

4. How Does Radiation Damage Occur?

5. Ionization • Ionizing Radiation can remove tightly bound electrons from their atomic orbits • This causes the atom to become charged or ionized • The atom can then react with neighboring atoms, forming new chemical bonds

6. Interactions with Cell Materials • Biological damage occurs due to chemical changes caused by ionization at the cellular level • Charged particles can ionize directly • X-rays must first undergo interactions to produce free electrons, which can then ionize

7. DNA is the primary target for biological damage!

8. Radiation Damage Mechanisms 1. Direct Action: Direct ionization of the DNA molecule, which may result in genetic damage. 2. Indirect Action: Radiation ionizes water, which causes free radicals to form. Free radicals attack targets such as DNA. Much more common.

9. Possible Effects to Cells • Radiation may pass through cell without doing any damage. • Damage may occur but be repaired. • The damaged cell may reproduce in its damaged form. • The cell may die.

10. Damage and Recovery • Single-strand breaks • Most DNA damage is repaired, with no long-term effects • Double-strand breaks • Not as easily repaired, more potential for long-term damage • Comparatively rare (about 1 DSB to 25 SSB)

11. Undamaged Cell

12. Damaged Cell

13. Determinants of Biological Effects • Rate of Absorption • Area exposed • Variation in Species and Individual Sensitivity • Variation in Cell Sensitivity

14. Cell Sensitivity The degree of cell sensitivity is directly related to the reproductive capacity of cells and tissues, thus stem cells (germ cells) are more radiosensitive than mature differentiated cells Law of Bergonie and Tribondeau Radiosensitivity is: • directly proportional to growth rate • indirectly proportional to degree of specialization

15. Cell Sensitivity Most Sensitive White Blood Cells (Lymphocytes) Red Blood Cells Epithelial Cells (Intestinal tract, Skin) Muscle Cells Least Sensitive Nerve Cells

16. Damage from Radiation Exposure • Acute • High dose in short time • Local: burns, hair loss, desquamation, blistering, damage to blood vessels, sterility, cataracts • Whole-body: reduction in blood cell counts, nausea, radiation sickness • Chronic • Low dose over long period of time • Cancer, anemia, cataracts

17. Appearance of Biological Effects • Prompt/Acute effect – effects seen immediately after large doses of radiation are delivered over a short period of time • Examples: radiation sickness and burns • threshold of 50 rad • Delayed effects- may appear months or years after a radiation exposure • Examples: cataract formation and cancer induction • threshold depends on effect (may be no threshold)

18. ACUTE RADIATION SYNDROME Response to an acute, total body, large radiation exposure

19. Stages in Acute Radiation Syndrome • Prodrome – initial sickness • Latent Stage – temporary recovery (feel better) • Manifest Illness Stage – symptoms depend on dose • Recovery or Death

20. Whole Body Exposures • The LD50/30 concept • Lethal Dose • 50% of population • 30 days • used for animal species • LD50/60 for humans • about 300-400 rad if no treatment is given

21. Dose / Radiation Syndrome Relationship • Dose < 1000 rad – white blood cells • Hematopoietic form • Dose > 1000 rad - epithelial cells • Gastrointestinal form • Dose > 10,000 rads - nerve cells • Cerebrovascular form

22. Hematopoietic Syndrome • Prodromal Stage: Mild symptoms appear within a few hours and last for several days • Latent Period: May last up to 4 weeks • Manifest Illness: Vomiting, diarrhea, fatigue and fever – Decline in blood cells – Recovery in 2 to 4 weeks…May last up to 6 months • Possible death due to infection, dehydration or hemorrhage

23. Gastrointestinal Syndrome • Prodromal Stage: Vomiting and diarrhea occur within hours and last up to one day • Latent Period: Lasts 3-5 days • Manifest Illness: Nausea, vomiting and diarrhea – Worsens to bloody stools • Death within 4 to 10 days after exposure primarily due to intestinal cell damage – Also damage to blood-forming tissue results in hemorrhaging and dehydration.

24. Central Nervous System Syndrome • Prodromal Stage: Severe nausea and vomiting within a few minutes – Nervousness, confusion, burning skin, vision loss, possible loss of consciousness • Latent Period: May last up to 12 hours, or not at all • Manifest Illness: Disorientation, loss of muscle control, breathing problems, seizures, coma • Death within a few days of exposure – due to increased fluid in brain (pressure) – Death occurs before hematologic and gastrointestinal symptoms appear

25. ACUTE LOCALIZED EFFECTS • Injury can also be caused when only localized areas of the body are exposed • Most common effects are skin-related: • 200 rad: mild erythema (reddening) • 300 rad: temporary hair loss • 600 rad: more severe erythema 10-14 days after exposure • 700 rad: permanent hair loss • 1000 rad: desquamation (shedding of skin) and tissue necrosis

26. Radiation Dermatitis (Case 1) • 57 y/o woman with 12-year history of red, painful, pruritic patch of skin located on her right subscapular area • Initial diagnosis was localized scleroderma

27. Progression of Injury • One week post-procedure, patient noted redness and itching • During following weeks, the patch enlarged and blisters appeared • Over the years, the patch became more violaceous and atrophic with increased itching and pain

28. Case #2 • 49 y/o man who underwent two transjugular intrahepatic portosystemic shunt (TIPS) procedures and one attempted TIPS placement within one week • Picture shown here is 6 months later • Ulceration with surrounding rings of de- and hyperpigmentation

29. Case #2 • 7.5 months after procedure • Small blisters developed • Wound is very painful

30. Case #2 • 10 months post-procedure • Wound has progressed in size and depth

31. Case #2 • 22 months post-procedure • Nonhealing ulcer with exposure of deep tissues, including spinous process of vertebra

32. Case #2 • 23 months post-procedure • Musculocutaneous skin grafting was performed

33. LONG TERM EFFECTS Delayed effects due to previous acute high dose exposures or from chronic low dose exposure over many years. • Carcinogenic • Embryological • Cataractogenic • Life span shortening

34. Genetic Effects • Genetic effects = heritable mutations to DNA • Seen in mammals but no convincing evidence in humans • Very difficult to measure due to subtle effects, long lifespans, uncertainties in background rate, and confounding factors • Japanese bomb survivors • 77,000 births with no substantial evidence of genetic effects

35. Human Evidence of Radiation Carcinogenesis • Radium dial painters • Radiologists and dentists • Uranium miners • Atomic bomb survivors • Patients receiving medical procedures

36. ANNUAL DOSE LIMITS

37. State Annual Limits • Occupationally Exposed Workers • 5 rem/yr whole body, gonads • 15 rem/yr lens • 50 rem/yr other organs, hands • Non-occupationally exposed worker (and the general public) • 0.1 rem /yr (100 mrem)

38. Origin Of Annual Limits Occupational dose limits were set an order of magnitude lower than the lowest level at which biological effects were observed.

39. UF Guidelines • Badged radiation workers will be contacted by a Radiation Control physicist when dose is: • Over 40 mrem/month for employees working with irradiator or in research labs • Over 300 mrem/month for employees working with x-ray units in medical or veterinary settings • Unusual for you or your work area

40. PREGNANT WORKERS

41. EFFECTS ON EMBRYO AND FETUS • Embryonic/fetal cells are rapidly dividing! • High sensitivity • Higher probability that damage will be reproduced over a large number of cells • Effects depend on stage of gestation

43. REGULATIONS FOR PREGNANT WORKERS 1. Limit embryo/fetus dose equivalent to 500 mrem (0.5 rem) total. 2. Once a pregnancy becomes known limit embryo fetus dose equivalent to 50 mrem per month, excluding medical exposure 3. Wear two personnel monitors. Fetal monitor under apron at waist. Maternal, outside apron at collar.

44. FEDERAL GUIDELINES FEDERAL REGISTER 1/27/87 “The health protection objectives…for the unborn should be achieved in accordance with the provisions of Title VII of the Civil Rights Act of 1964…with respect to discrimination in employment practices.” -VOLUNTARY declaration of pregnancy to employer as soon as soon as possible.

45. FEDERAL GUIDELINES FEDERAL REGISTER 1/27/87 Protection of the unborn is a joint responsibility of the employer and the worker. Protection through: Use of protective equipment, worker self selection, and temporary job rotation.

46. LOOKING AT RISK

47. Types of Risk Models • Stochastic (LNT) • Probability, but not severity, of effect increases as dose increases • Usually uses linear no threshold (LNT) model • Non Stochastic or Deterministic Effects • Severity of effect increases as the dose increases • Model has a threshold and may or may not be linear No threshold Threshold

48. Cancer Risk from Chronic Exposure From the NRC: • LINEAR - An increase in dose results in a proportional increase in risk • NO-THRESHOLD - Any dose, no matter how small, produces some risk • The risk does not start at 0 because there is some risk of cancer, even with no occupational exposure. • Exposure to radiation is not a guarantee of harm. However, because of the linear, no-threshold model, more exposure means more risk, and there is no dose of radiation so small that it will not have some effect.

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