(Jeffrey Mahn) USofA - Biological Effects of Radiation

Biological Effects of Radiation J.A. Mahn

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Outline • Historical perspective of human radiation exposures • Some radiation and radiation exposure basics • Ingestion of radionuclides and types of biological effects • Radiological dose and dose rate • Biological effects of radiation • Dose-response regimes 2

Historical Perspective of Radiation • First observance of ionizing radiation (x-rays) by Wilhelm Roentgen in 1895 • Possible use of ionizing radiation for medical diagnostics proposed by Roentgen in 1896 • Beneficial, or hormetic, effects of low doses of ionizing radiation observed by 1898 • Effectiveness of “radium rays” for cancer therapy recognized in 1902 • Early radiation “users” voluntarily/unknowingly exposed themselves to high doses 3

Historical Perspective of Radiation (cont.)

• Death of English radiotherapist from overexposure in 1906 led to first radiation hysteria • By 1922 about 100 deaths occurred from afflictions that could be related to ionizing radiation exposure • Radium poisoning case (drug overdose) occurred in 1932 – Philadelphia industrialist and socialite Eben Byers died from massive overdose of radium ingested in large quantities over three years – Generated great publicity and created great public fear of radiation 4

Historical Perspective of Radiation (cont.)

• Abrupt change in public mood regarding radiation after WW II due to political and social issues related to radioactive fallout from nuclear weapon testing, not real radiation effects • Evidence of harm from radiation exposure almost entirely related to relatively short-term (acute) exposures to high doses; in particular – people exposed during bombings of Hiroshima and Nagasaki – medical uses of x-rays during first half of 20th century 5

Ionizing & Non-Ionizing Radiation • Ionizing Radiation: Energy transmitted as particles or electromagnetic waves with sufficient energy to dislodge orbital electrons from atoms, thereby producing ions.

▪ Examples: alpha, beta, gamma, neutron, and xray

• Non-ionizing Radiation: Energy transmitted as electromagnetic waves with insufficient energy to dislodge orbital electrons from atoms; produces a heating effect in body tissue.

▪ Examples: visible light, infra-red, micro-waves, radio-waves, and radar

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Why We Are Concerned About Radiation Ionizing Radiation Human Cells Atoms in Cells Form Ions No Change in Cell

Malignant Growth

Change in Cell

Cell Dies

Reproduces

Replaced

Benign Growth

Not Replaced 7

External Background Radiation • Natural background radiation varies around the world US Average -- 350 mrem/y Cosmic Terrestrial Internal (K-40) Inhaled (Radon) Medical/Etc.

30 mrem/y 30 mrem/y 40 mrem/y 200 mrem/y 50 mrem/y

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Biological (Internal) Radionuclides • Potassium and carbon, essential elements that make up the human body, contain radioactive K-40 and C-14 (both β emitters), respectively • Largest component of this annual radiation exposure is from K-40 US Average -- 350 mrem/y Cosmic Terrestrial Internal (K-40) Inhaled (Radon) Medical/Etc.

30 mrem/y 30 mrem/y 40 mrem/y 200 mrem/y 50 mrem/y 9

Internal Exposure from Radon • Radon gas in air we breathe results from radioactive decay of uranium and thorium in earth’s crust (varies around the world) • Inhaled radon (α emitter) is largest contributor to US average annual radiation exposure US Average -- 350 mrem/y Cosmic Terrestrial Internal (K-40) Inhaled (Radon) Medical/Etc.

30 mrem/y 30 mrem/y 40 mrem/y 200 mrem/y 50 mrem/y 10

Zone 1 counties have a predicted average indoor radon screening level greater than 4 pCi/L (pico curies per liter) (red zones)

Highest Potential

Zone 2 counties have a predicted average indoor radon screening level between 2 and 4 pCi/L (orange zones)

Moderate Potential

Zone 3 counties have a predicted average indoor radon screening level less than 2 pCi/L (yellow zones)

Low Potential

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Manufactured sources of radiation contribute an average of 60 mrem/year cigarette smoking - 1300 mrem

medical - 53 mrem

round trip US by air 5 mrem per trip

building materials - 3.6 mrem

smoke detectors - 0.0001 mrem 12

Natural Radiation Exposures • No evidence of increased cancers among people living in areas where natural background radiation is much higher than average ➢ average annual dose in Araxa, Brazil is 2,450 mrem* ➢ annual dose in State of Kerala, India as high as 7,640 mrem* ➢ annual dose in Guarapari, Brazil as high as 17,500 mrem ➢ annual dose in Ramsar, Iran as high as 26,000 mrem*

* Ref. Nuclear Report, 21st Century, Winter 2000-2001, pages 10-16

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Ingestion of Radionuclides • Ingestion is the most important route for

introduction of radionuclides into organisms • Insoluble radioactive compounds are not absorbed from GI tract and cause only local irradiation before being excreted • Soluble radioactive compounds show wide range of GI absorption percentages

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GI Absorption of Radionuclides Isotope

Radiation Half-life GI Absorption

Hydrogen-3 (Tritium)

β

12 years*

100%

Strontium-89

β

51 days

30%

Strontium-90/Yttrium-90

β

29 years

30%

Zirconium-95/Niobium-95

β,γ

64 days

0.01%

Ruthenium-103

β,γ

39 days

0.03%

Ruthenium-106/Rhodium-106

β,γ

1 year

0.03%

Iodine-131

β,γ

8 days

100%

Cesium-137

β,γ

30 years

100%

Barium-140/Lanthanum-140

β,γ

13 days

5%

Cerium-141

β,γ

33 days

0.01%

Cerium-144/Praseodymium-144

β,γ

285 days

0.01%

3 years

0.01%

Promethium-147

β

* Tritiated water can be absorbed through the skin

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Biological Radionuclide Removal Pathways Soluble

Insoluble

Stomach

Stomach

30%

Small intestine

Blood

Small Intestine

28%

2% Kidney

Large Intestine

Large Intestine 100%

70% Feces

Sweat + Exhalation

Urine

Feces

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Effective Half-Lives of Common Radionuclides Radionuclides Hydrogen-3 Carbon-14 Phosphorus-32 Sulfur-35 Chromium-51 Manganese-54 Iron-59 Cobalt-58 Cobalt-60 Zinc-65 Rubidium-87 Strontium-90 Technetium-99m Iodine-131 Cesium-134 Cesium-137 Iridium-192 Gold-198 Mercury-203 Radon-222 Radium-226 Uranium-235 Plutonium-239

Physical Half-Life (Days) 4.5x103 2.1x106 14.3 87.1 27.8 300 45.1 72 1.9x103 245 1.8x1013 1.0x104 0.25 8 840 1.1x104 74.5 2.7 45.8 3.83 5.9x105 2.6x1011 8.9x106

Biological Half-Life (Days) 12 40 1155 90 616 25 600 9.5 9.5 933 60 1.8x104 20 138 70 70 20 120 14.5 None 1.64x104 300 7.3x104

Effective Half-Life (Days) 12 40 14.1 44.3 26.6 23.1 41.9 8.4 9.5 194 60 6.4x103 0.25 7.6 64.6 70 15.8 2.6 11 3.83 1.6x104 300 7.2x104

1/te = 1/tp + 1/tb

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Biological Effects Factors • •

Certain body parts more specifically affected by exposure to different types of radiation sources Potential health effects of radiation exposure depend upon – Dose (amount of energy deposited in body organs) – Ability of the radiation to harm human tissue (i.e., radiation type) – Which organs are affected

•

Most important factor is dose - amount of energy actually deposited 19

Critical Organs for Selected Radionuclides Radioisotope Hydrogen-3 (Tritium) Phosphorous-32 Carbon-14 Sulfur-35 Chromium-51 Cobalt-60 Zinc-65 Rubidium-87 Strontium-89, 90 Yttrium-91 Technetium-99m Ruthenium-103, 106 Iodine-125, 131 – 135 Tellurium-129m Cesium-137 Cerium-144 Gold-198 Mercury-203 Iridium-192 Radon-222 Radium-226 Uranium-235 Plutonium-239

Critical Organ Whole Body Bone Fat Testes, Whole body Lower Intestine Lower Large Intestine Liver, Prostate Pancreas Bone Bone Upper Large Intestine Kidney Thyroid Kidney Whole body, Liver, Spleen Bone Lower Large Intestine Kidney Lower Large Intestine Lung Bone Lower Large Intestine Bone 20

Types of Biological Effects • Biological effects of radiation can be broken into two groups according to how responses (symptoms or effects) relate to dose (amount of radiation received) – Stochastic (probabilistic) effects – Deterministic (dose dependent) effects

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Stochastic Effects • Stochastic effects are those effects which have an increased probability of occurrence with increased dose, but whose severity is unchanged • Example: skin cancer and sunlight – the probability of getting skin cancer increases with increasing exposure to the sun • Stochastic effects are like a light switch; they are either present or not present 22

Deterministic Effects • Deterministic effects are those responses which increase in severity with increased dose • For example: sunburn – the more you’re exposed to the sun, and the higher the ‘dose’ of sunlight you receive, the more severe the sunburn • Acute radiation syndrome is a deterministic effect of ionizing radiation – occurs above a threshold dose and severity increases with dose 23

Schrödinger’s Cat Activity

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Dose Rate • Acute Dose – Dose delivered over a short period of time (e.g., chest xray)

• Chronic Dose – Dose delivered over an extended period of time (e.g., natural background)

• Dose Rate Effect – Acute dose generally more damaging than chronic dose of same magnitude because short-term cell damage overwhelms body’s natural repair mechanisms

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Biological Effects of Radiation • Biological cell/tissue damage dependent upon – Dose & dose rate (acute or chronic) – Direct effects (interactions with atoms of DNA and cellular components critical to survival of cell) – Indirect effects (break less critical molecules into reactive parts) 26

Biological Effects of Radiation (cont.)

• Hierarchy of cell susceptibility to damage (highest to lowest) – – – – – – –

Lymph Blood Reproductive and gastrointestinal Bone Nerve Brain Muscle

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Biological Effects of Radiation (cont.) • Chronic exposure of adults to radiation at average rates up to approximately a hundred times natural background may be incurred for many years without observable health effects • Possible consequences of chronic exposure at rates several hundred times background are 1) leukopenia (deficient white cells), 2) anemia (deficient red cells), 3) detrimental changes in tissue structure, 4) leukemia, 5) malignant tumors, 6) cataracts, and 7) increased rate of genetic mutation 28

Biological Effects of Radiation (cont.) • Harmful effects caused by ionization (and excitation) in cells composing living tissue – Breaking of chromosomes, swelling of cell and cell nucleus, increase in viscosity of cell fluid, increase in permeability of cell membrane, and cell destruction

Ref. The Effects of Nuclear Weapons, US DoD and US DOE, Third Edition, 1977 29

Biological Effects of Radiation (cont.)

• Harmful effects caused by ionization/excitation (cont.)

– Products formed in cell may act as poisons (free radicals) – Reactive Oxygen Species (ROS) primary culprit in DNA radiation damage Ref. The Effects of Nuclear Weapons, US DoD and US DOE, Third Edition, 1977 30

Biological Effects of Radiation (cont.)

• Harmful effects caused by ionization/excitation cont.)

– Process of cell division (mitosis) may be delayed by radiation exposure so normal cell replacement inhibited

Ref. The Effects of Nuclear Weapons, US DoD and US DOE, Third Edition, 1977 31

DNA is Most Important Molecule That Can be Changed by Radiation Effects of DNA Damage

Gene Expression A gene may respond to the radiation by changing its signal to produce protein. This may be protective or damaging.

Cell Destruction

Chromosome Aberrations Gene Mutation Sometimes a specific gene is changed so that it is unable to make its corresponding protein properly.

Sometimes the damage affects the entire chromosome, causing it to break or recombine in an abnormal way.

Sometimes parts of two different chromosomes may be combined.

Genomic Instability Sometimes DNA damage produces later changes which may contribute to cancer.

Damaged DNA may trigger apoptosis, or programmed cell death. If only a few cells are affected, this prevents reproduction of damaged DNA and protects the tissue.

Studies have shown that most radiation-induced DNA 32 damage is normally repaired by the body

DNA Strand Breaks Occur Frequently Ionized oxygen molecules from metabolism are the principal causes.

Double strand breaks occur 10 times per day per cell.

Single strand breaks occur 10,000 times per day per cell.

100 mSv/y radiation adds 1 per year.

100 mSv/y radiation adds 12 per day.

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DNA Repair Special enzyme encircles double helix to repair broken strand of DNA DNA repair times are ~1 hour

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Radiation Effects in Perspective • DNA in human cells also damaged by normal biological functions (routine eating, breathing, stress of heat and exercise) • Gene mutations (unrepaired or mis-repaired DNA damage) from normal metabolism outnumber those caused by natural radiation by 107 • Even high radiation doses add only a few more gene mutations to millions occurring from normal metabolism Ref. James Muckerheide, paper presented at the 8th International Conference on Nuclear Engineering, held in Baltimore, April 2-6, 2000 35

What causes Cancer?

Radiation is not a big hitter!!!

Cigarette smoke Diet & nutrition Chronic infection Occupational exposure Genetic Alcohol drinking

WHO

Environmental factors including radiation 36

Whole Body Effects from Internal Radioactivity Exposures

ARS = acute radiation syndrome 1 kBq = 2.7x10-2 µCurie

Decay modes: Cs-137 – β/γ, Po-210 – β/γ, Ra-226 – α/γ, K-40 – β/γ

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Explanatory Notes for Previous Table The previous table illustrates whole-body effects of internal radioactivity, in descending order of isotope activity. Internal doses in red were fatal, those in pale yellow marginal, those in green harmless. Beta emitters Cs-137 [6][7][9] and K-40 [12] may be compared directly, but Polonium (Litvinenko [10]) and Radium (dial painters [11]) are alpha emitters producing greater internal damage.

References

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Explanatory Notes for Previous Table

References

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Dose-Response Dose: 0-10 rem (0-100 mSv)

Acute/Chronic Dose Response: No observable detrimental health effects (effects either nonexistent or too small to observe) • Natural background – 0.3 rem (3 mSv) • Medical diagnostic procedures ➢ 0.01 rem (0.1 mSv) – full-mouth dental x-rays, chest x-ray ➢ 0.1 rem (1 mSv) – spinal/pelvic/hip x-ray, mammogram ➢ 0.5 rem (5 mSv) – kidney/spinal series x-rays, barium-related x-rays, head CT scan, most nuclear medicine brain, liver, kidney, bone, or lung scans ➢ 1 rem (10 mSv) – barium enema (large intestine) x-rays, chest/abdomen/pelvic CT scans ➢ 5 rem (50 mSv) – heart x-rays, most nuclear medicine x-rays

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Dose-Response (cont.)

Position statement of Health Physics Society* • Radiogenic health effects (primarily cancer) demonstrated through epidemiological studies only at acute doses exceeding 100 mSv • Estimation of adverse health effects below (acute) dose of 100 mSv remains speculative • Epidemiological studies have not demonstrated adverse health effects for doses less than 100 mSv delivered over period of many years (chronic dose) * Radiation Risk in Perspective, Position Statement of the Health Physics Society; Adopted January 1996, Revised July 2010

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Dose-Response (cont.)

Dose: 10-50 rem (100-500 mSv)

Acute Dose Response: • Short-term blood cell decreases for ~ 50 rem doses • No valid epidemiologic or experimental data to support linearly extrapolated predictions of cancer from higher dose cancer data

Chronic Dose Response: • Stimulates immune system defenses • Prevents oxidative DNA damage • Epidemiological studies and scientific data show decreased risk of cancer 43

Dose-Response (cont.)

Dose: 50-100 rem (0.5-1 Sv)

Acute Dose Response: • Nausea and fatigue • Delayed effects – slightly increased cancer risk

Chronic Dose Response: • No observable detrimental health effects (effects either non-existent or too small to observe)

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Dose-Response (cont.)

Dose: 100-300 rem (1-3 Sv)

Acute Dose Response: • Radiation sickness (nausea, vomiting, diarrhea, reduced lymphocyte cell count) within ~ 48 hours • Destruction of blood, GI tract, reproductive, and hair cells; DNA/RNA damage in surviving cells • Delayed (long-term) effects ➢ Leukemia/lymphoma/cancer ➢ Cataracts ➢ Genetic defects ➢ Blood disorders ➢ Lifespan shortening 45

Dose-Response (cont.)

Dose: 300-500 rem (3-5 Sv)

Acute Dose Response: • Radiation sickness occurs within hours • Loss of hair and appetite occurs within a week • Statistically, half of exposed population will die without medical attention

Dose: 500-1200 rem (5-12 Sv)

Acute Dose Response: Death within a few days • 1,000 rem (10 Sv) given over several days to destroy bone marrow in preparation for marrow transplant 46

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Biological Effects Summary • Ingestion is most important route for introduction of radionuclides into organisms • Certain body parts more specifically affected by exposure to different types of radiation sources • Potential health effects of radiation exposure depend upon radiation type, dose, and affected organ(s)

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Biological Effects Summary (cont.)

• Effects depend upon how biological responses relate to dose ➢ Stochastic effects – increasing probability of occurrence with increasing dose ➢ Deterministic effects – increasing severity of response with increasing dose

• Harmful effects caused by ionization (and excitation) in cells composing living tissue

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Biological Effects Summary (cont.)

• Possible consequences of chronic exposure at rates several hundred times background: ➢ Leukopenia ➢ Anemia ➢ Detrimental changes in tissue structure ➢ Leukemia ➢ Malignant tumors ➢ Cataracts ➢ Increased rate of genetic mutation

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Biological Effects Summary (cont.)

• DNA is most important molecule that can be changed by radiation • Studies have shown most radiation-induced DNA damage normally repaired by the body

• Gene mutations (unrepaired or misrepaired DNA damage) from normal metabolism outnumber those caused by natural radiation by 107

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Additional References References from Muckerheide paper • M. Bishop, 1989. “Cancer,” in Molecular Biology of the Cell, eds.

Bruce Alberts, et al., Chap. 21, pp. 1187-1218 • D. Billen, 1990. “Spontaneous DNA Damage and Its Significance for the ‘Negligible Dose’ Controversy in Radiation Protection,” Radiation Research, Vol. 124, pp. 242-245 • H. Varmus, and R.A. Weinberg, 1993. “Genes and the Biology of Cancer,” Scientific American Library, Vol. 153

Dose-Response information – Health Physics Society Miller, D.W., Jr., MD, Afraid of Radiation? Low Doses are Good for You, April 2, 2004

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Backup Slides

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Kerala India Study • Kerala’s monazite sand – contains 1/3 of world’s economically recoverable reserves of thorium (Th-232) – emits ~ 8 μSv per hour of gamma radiation (> 7000 mrem/year)

• Decade long study of 69,985 residents* – published in Health Physics in 2009 – showed no excess cancer risk (actually, slightly reduced cancer risk) * Ref. Nair, R; et al. (2009-01-01). "Background radiation and cancer incidence in Kerala, India-Karanagappally cohort study,“ Health Physics 96.

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Correcting a Radiation Exposure Misconception • Exposure to gamma radiation does not make

humans, animals, or food radioactive • Only way to make an atom radioactive is to change ratio of neutrons to protons in atomic nucleus • Gamma-rays have no effect on numbers of neutrons and protons in atomic nuclei

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Absorbed Dose (Exposure) • Dependent on effective half-life of radionuclide • Radiation Absorbed Dose (rad) – energy absorbed per unit mass of irradiated material (10-5 Joules per gram)

• International (SI) Unit – Gray [Gy] 1 Gy = 100 rad

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Dose Effects • Depend on Absorbed Dose and Linear Energy Transfer (LET)

Radiation Alpha particles Beta particles Gamma rays

Relative Range 1 100 10,000

Relative LET 10,000 100 1

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What Does This Mean?

Radiation & Range in Air Energy Deposition Alpha (4-5 MeV)a

1-2 inches

Beta – 0.1 MeV 1.0 MeVb 3.0 MeV

4 inches 12 feet 43 feet

Notes: a. Alpha energy associated with Uranium, Thorium, and Plutonium decay b. Average maximum energy of beta particles from fission products is about 1.2 MeV

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Dose Effects (cont.) • Effect on Biological Systems Quantified Using Relative Biological Effectiveness [RBE] • RBE defined as dose of 250-keV x-rays producing given effect divided by dose of reference radiation for same effect Radiation X-rays Gamma radiation Beta particles Thermal neutrons Fast neutrons Alpha particles

RBE Factor 1 1 1 5 10 20 59

Equivalent Dose • Represents potential for biological effects • Historical/Conventional Unit Dose (rem) = RBE x Dose (rad)

• International (SI) Unit – Sievert [Sv] Dose (Sv) = RBE x Dose (Gy) • For gamma rays and x-rays (RBE = 1)

1 Sv = 1 Gy = 100 rem

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Biological Effects of Radiation (cont.)

Scheme of particle distribution in tissues. Shown are several electrons and an alpha particle. Clearly, total energy absorbed per unit mass (i.e., dose) correlates with the number of particles in that mass.

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Radiation Attenuation 



++  

−

 1

−



0n

Paper

Plastic

Lead

Concrete

Alpha

Beta

Gamma and X-rays

Neutron

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Decay Scheme for Cobalt-60

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Average Annual Dose- United States

Radon Cosmic Terrestrial Internal Medical X-rays Nuclear Medicine Consumer Products Other

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NRC Administrative Limits Subjects Exposed

Time Frame

Dose (mrem)

Nuclear Worker

1 year

5000

General Public (from nuclear facility)

1 year

100

9 months

500

Pregnant Woman

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Radiation Exposure • Dose comparisons ➢ Cross country airplane flight – 4 mrem/flight ➢ Consumer products – 10 mrem/year ➢ NRC occupational limit – 5,000 mrem/year ➢ EPA acute dose for <1% increased cancer risk – 10,000 mrem ➢ Acute dose causing radiation sickness – 50,000 to 100,000 mrem ➢ LD50 acute dose – 450,000 to 500,000 mrem

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Human-made vs Natural Radiation Dose Per Year mSv Rem 50 5 Guarapari beach, Brazil: up to 790 mSv Ramsar, Iran: up to 700 mSv Southwest France: up to 88 mSv

To More Than 700 mSv mSv 1.0

Rem 0.10

0.8

0.6

0.4

0.08 GLOBAL AVERAGE INDIVIDUAL WHOLE BODY RADIATION DOSE (Each Year)

Medical Diagnostics

0.06

0.04

NATURAL BACKGROUND RADIATION

Lower End of Natural Background Radiation 40

4

Kerala beach, India: up to 35 mSv

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3

Araxรก, Brazil: up to 25 mSv

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2 Sweden: up to 18 mSv

0.2

Adapted from Z. Jaworowski's paper at the "International Conference on Radiation," Teheran, Iran, Oct 18-20, 2000, based on UNSCEAR figures.

0.02 Nuclear Explosions

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1

US Rocky mountain states: 6-12 mSv

Chernobyl 0

Nuclear Power

Evacuated land near Chernobyl: 6 mSv US Capitol & Grand Central Station, NYC: 5 mSv

0

1940 1950 1960 1970 1980 1990 2000 YEAR

World average: 2.4 mSv San Francisco, US Gulf states: 0.8-1.2 mSv 0

0

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Effects of Radiation At low doses, such as what we receive every day from background radiation, the cells repair the damage rapidly. At higher doses (up to 100 rem), the cells might not be able to repair the damage, and the cells may either be changed permanently or die.

Most cells that die are of little consequence, the body can just replace them. Cells changed permanently may go on to produce abnormal cells when they divide. In the right circumstance, these cells may become cancerous. This is the origin of our increased risk in cancer, as a result of radiation exposure.

At even higher doses, the cells cannot be replaced fast enough and tissues fail to function. An example of this would be "radiation sickness." This is a condition that results after high doses to the whole body (>100 rem), where the intestinal lining is damaged to the point that it cannot perform its functions of intake of water and nutrients, and protecting the body against infection. This leads to nausea, diarrhea and general weakness. With higher whole body doses (>300 rem), the body's immune system is damaged and cannot fight off infection and disease. At whole body doses near 400 rem, if no medical attention is given, about 50% of the people are expected to die within 60 days of the exposure, due mostly from infections.

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Lymphatic System

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