Biological Effects of Ionizing Radiation Science of Nuclear Energy and Radiation Science Teacher Workshop University of Richmond Richmond, VA July 18, 2007 Biological Effects of Ionizing Radiation Carl A. Tarantino, CHP Corporate Health Physicist Dominion Generation

Radiation in Life Radon Solar Radiation Cosmic Rays Nuclear Medicine X-Rays  Radon Consumer Products Each Other Many sources of radiation all around us. Natural and man-made. Cosmic – 26 mrem Terrestial – 274 mrem (200 from radon) Medical & Consumer products – 60 mrem Nuclear Power – 0.1 mrem/year Total annual to public – 360 mrem Radioactive Waste Nuclear Power Food & Drink Terrestrial Radiation

Ionizing Radiation Units Old Units SI Units What It Is 1 C kg-1 = 3876 R rad Gray 1 Gy = 100 rad rem Sievert 1 Sv = 100 rem Traditional units are still used in US today; SI – System International Coulomb – unit of electric charge Absorbed dose, D, is related to dose equivalent, H, by: H = D x Q, where Q – quality factor, which takes into account the relative amount of biological harm done by the various types of radiation. Typical QFs are: Alpha = 20 Beta, x-ray, gamma = 1 Neutron (energy dependent) thermal (slow) – 3; fast – 10

Measuring Radiation Effects How much radiation is produced Activity: decays per time (Curie (Ci), Becquerel (Bq)) How much energy absorbed by tissue Dose How much biological damage does the radiation do per energy absorbed Dose equivalent Traditional units are still used in US today; SI – System International Coulomb – unit of electric charge

Ionizing Radiation Effects Absorption of Radiation Ionization Chemical Change Repair or Damage Discuss in general terms High Dose Effects Cell killing Tissue or organ effects Whole body effects Low Dose Effects Mutations Cancer Effects to unborn

Cellular Organization Radiation removes an electron from an atom Atoms join to form molecules Molecules as a group form a cell Cellular – cell structure Cell membrane – 3-5K rad – cell membrane ruptures >3k rad – affects cell permeability Organelles – radiation damage reduces organelles’ ability to synthesize and metabolize; mitochondria – at a few 1000 rads, function is disrupted- this interferes with ATP production (energy) Lysosomes – rupture at 500 – 1000 rad; releases digestive enzymes into cell (cell suicide) Nucleus – most radiosensitive part of the cell Major effect on nucleus – inhibition of DNA/RNA production, preventing cell division Damage to genetic material can cause cell to become cancerous Cells Tissue Organ Organism

Potential Radiation Damage to DNA Most critical molecule within humans: DNA Direct effect on molecule by ionization or excitation of the molecule and subsequent dissociation of the molecule Radiation affects the DNA in cells. DNA controls the cell’s function and ability to reproduce May destroy the DNA , i.e. kill the cell May damage the DNA; the cell can: repair itself, not function at all or not function properly, or undergo uncontrolled division (cancer) DNA is long strand of small molecules Directly or indirectly, radiation affects the DNA in cells

Other Damage to DNA Many other entities cause breaks in DNA Temperature, chemicals, etc. Human DNA suffer millions of DNA breaks daily Most repaired Radiation affects the DNA in cells. DNA controls the cell’s function and ability to reproduce May destroy the DNA , i.e. kill the cell May damage the DNA; the cell can: repair itself, not function at all or not function properly, or undergo uncontrolled division (cancer)

Radiation Induced Decomposition of Water Within a Cell Most abundant molecule within humans: Water H2O H2O+ H2 e- H+ Incoming Radiation WATER OH- Ho Hydrolysis and the production of radicals Water is 70% – 80% soft tissue Radiation can directly ionize water molecules Further effects are produced indirectly when radicals form compounds that interact with cell material Free radical is neutral – same number of electrons and protons, but are chemically reactive due to unpaired electron in outer shell Radicals have a high potential to form stable organic peroxides, often denaturing molecules HO2 H2O2 OHo Production of free radicals within the cell can result in indirect effects

Potential Outcomes of Radiation Damage to Parent Cells Introduce cancer cells due to uncontrolled growth. All radiation interactions do not result in cancer. Estimated that within a person’s body 10,000,000 cells are struck by ionizing radiation per minute from naturally occurring radioactive isotopes (e.g. K-40, C-14) and background radiation Cells have a high capability for repair through the action of the cell itself or replacement of badly injured cells by mitosis of healthy cells.

Cell Repair after Chronic Dose Damage Radiation Dose Repair is dependent upon: LET – linear energy transfer (kev per micron) Radiation type Dose fractionation Dose rate Total absorbed dose It is thought that chronic exposure allows for significant cell repair, but may build up a certain level of irreparable damage Reparable Accumulated Irreparable Time

Cellular Radiosensitivity: Law of Bergonie and Tribondeau The basic law of Bergonie and Tribondeau is that young and rapidly dividing cells are more sensitive than cells with adult development. Cells tend to be radiosensitive if they have three properties: Cells that have high division rate (the time between divisions) Cells that have long dividing future (immature cells in early cellular life) Cells that are unspecialized (cells which have a widely diverse future) Human ova and sperm meet all 3 criteria. Rapidly dividing cells include bone marrow, hair, fetus, small intestine Cells least affected are slowly dividing cells such as nerve, muscle, brain

Relative Sensitivity of Cell and Tissue Types MOST SENSITIVE Lymphocytes Spermatogonia Hematopoietic (Blood Forming) Intestinal Epithelium Skin Nerve Cells Muscle Tissue Bone Collagen LEAST SENSITIVE

Hematological Response 1 Sv (100 rems) Hemolobin not affected Lymphocytes are most affected

Hematological Response 3 Sv (300 rems) RBCs are more affected from a delivered dose of 300 rem. Longer time for recovery

Possible Radiation Dose Response Curves Most conservative model: An increase in dose results in a proportional increase in risk At low doses there is only a slight increase in risk that becomes proportional to dose at higher doses There is a threshold for dose response at which lower doses do not result in increased risk At low doses there is a higher risk that becomes proportional to dose at higher doses Hormesis model (not shown): Low doses of radiation have a positive effect and decrease risk 1- Linear (Non-Threshold) 2 - Linear-Quadratic 3 - Threshold 4 - Supralinear Dose (rem) Effects Risk of health effects is known at doses above 10 rem; this risk is extrapolated to lower doses LNT – most conservative; dose is proportional to risk Linear Quadratic – at low doses, there is only a slight increase in risk that becomes proportional at higher doses Threshold – for dose response at which lower doses do not result in increased risk Supralinear – at lose doses there is a higher risk that becomes proportional to dose at higher doeses; this assumes low level, i.e. background levels, is more harmful than high dose medical procedures Area of uncertainty – recommend against quantitative estimation of health risks HPS/NCRP/NEI – position is that < 5 – 10 rem, risks of health effects are either too small to be observed or are non existent.

Hormesis Some data indicate that low doses of radiation are beneficial Not widely accepted Conservative is better But not impossible Assumes low level radiation is beneficial, like vitamins, resulting in increased life span, increased growth and fertility, reduction in cancer incidence

Risk Terms A large dose of radiation in a short period of time Small doses of radiation protracted over a long period of time Health effects that occur randomly and for which the probability of the effect occurring, rather than its severity, is assumed to be a linear function of dose without threshold Health effects which do not appear until a threshold value is exceeded and for which the severity of the effect increases with dose beyond the threshold Effects which occur in the exposed individual Effects which occur in the progeny of the exposed individual due to chromosome aberrations in the parent Effects to the unborn fetus irradiated in-utero Acute Chronic Stochastic Non-stochastic Somatic Genetic Teratogenic

Risk Examples Hereditary effects Cancer (leukemia, tumors) Erythema (skin reddening) Cataracts Sterility Epilation (hair loss) Hematological effects Genetic; stochastic Somatic; stochastic Somatic; non-stochastic First 2 risk examples are from chronic exposures The remaining risk examples are from acute exposures 25 – 100 rad = effects on the blood 300 rad low LET or 1000 high LET = erythema 500 rad = cataracts 300 rad for women and 600 rad men = permanent sterility 700 rad = permanent hair loss

Biological Effects from Low Doses of Radiation Biological effects from low doses potentially occur due to chronic exposures. A chronic exposure occurs when a relatively small amount of radiation is absorbed by tissue over a long period of time. Under 5 rad of exposure - No detectable health effects in exposed individual Chronic exposures result in an increased risk in latent adverse health effects Health effects could be genetic effects or somatic effects The biological effects that can show up years after exposure to radiation, called late effects, include various kinds of cancer in the exposed person and birth defects in the offspring of the exposed person. It is a fact that radiation can cause cancer and genetic effects. Increases in cancer above the normal level have been observed in people who have survived high doses of radiation. Genetic effects have been observed in animal studies which also involved high radiation doses. Neither of these effects has been proven in persons exposed to low doses of radiation. This does not mean that these effects don't happen. It means that, at low doses, if an increase in the number of cancers or birth defects occurs, it is small compared to the number that occur "normally".

Latency Period Time (years) Risk Time radiation dose received Latent period Period at risk Risk curve 4 30 Latency period is the time from time of exposure until the effect is exhibited Radiation exposure does not produce cancer in every exposed person Effects can be immediate or years later for acute, high-level exposures Latency period is short for leukemias, ( 2 – 4- years), compared to solid tumors Japanese A-bomb survivor peak incidence of leukemia occurred at 7 years after exposure; dropped back to “normal” at 25 years after exposure Solid tumor latency period is 10 – 30 years Leukemia latency and time at risk periods

Biological Effects from High Doses of Radiation Biological effects from high doses occur due to acute exposures. An acute exposure occurs when a relatively large amount of radiation is absorbed by tissue over a short period of time; effects can occur in the short term and long term. Hematopoietic Syndrome: (100-200 rad or 1-2 Gray) Early symptoms are anorexia, nausea, and vomiting followed by a phase of bone marrow depression and subsequent susceptibility to infection. After several weeks, death may occur. Gastrointestinal Syndrome: (700-1000 rad or 7-10 Gray) Early symptoms are anorexia, nausea, and vomiting followed by fever, diarrhea, and electrolyte imbalance due to ulceration of the intestinal wall. Once GI system ceases to function, death will occur. Central Nervous System Syndrome: (2000-5000 rad or 20-50 Gray) Symptoms occur very quickly and the brain and muscles can no longer control bodily functions, including breathing and blood circulation. Death within hours or within several days. The term acute dose is defined as a dose of radiation delivered over a short period of time. This does not necessarily mean that the dose is massive. By short, it means short compared to how quickly the body can overcome the damage to the cells and tissues. If the dose is both acute and large, early effects may be observed within a few hours or days. If this same dose is delivered over a long period of time it is called a chronic dose and no early effects will be seen because the body has the time to repair the damage before it builds up to a level at which we see effects. Both acute doses (if non-lethal) and chronic doses increase the risk of late effects such as cancer. The difference between an acute and chronic dose is somewhat arbitrary but, in general, doses received over less‑than four days to a week are considered acute. All others are considered chronic doses. The early effects that radiation can cause are often referred to as radiation sickness or collectively as the acute radiation syndrome. They include nausea, vomiting, diarrhea, general malaise, loss of appetite, infections, fever, internal bleeding and hemorrhage, and sometimes death. These effects have been observed in people who have received acute radiation doses which cause severe damage to the blood cells, bone marrow cells and the tissues lining the gut. This knowledge is based on actual human data as a result of accidental, therapeutic, and atomic weapon related exposures to high levels of radiation. Animal studies have added greatly to our knowledge of acute radiation effects. These early effects occur only for massive, acute doses of radiation, greater than 200 rem to the whole body. For example, 450 rem is the acute, whole body dose of radiation that would kill 50% of the people within sixty days after the exposure (with no medical care). Higher doses would cause a higher percentage of early deaths. Doses in excess of 600 rem would be fatal to most, if not all, persons exposed, without medical care. With heroic medical treatment, acute doses in excess of 600 rem to the whole body could be survived. Doses this high rarely occur and are usually a result of industrial accidents or war related exposures. Of more concern to us are the late effects that can be caused by lower doses of radiation.

Effects From Acute, High-level Radiation Doses These are effects from acute high level radiation doses of the Whole Body Note that lymphocytes are very radiosensitive Small intestines are very sensitive due to the crypt cells at the base of the villi and underlying capillary beds, which become depleted

Median Lethal Dose Curve Normal cancer incidence is ~55% of US citizens get cancer Normal mortality is ~25% of US citizens die from cancer Dose (rad) LD50 - Median Lethal Dose LD50/30 - Lethal dose to 50% of exposed population within 30 days of irradiation, without medical attention Defined at approximately 450 rad

What is Safe? Driving a car is “safe” 1:6,000 Living at home is “safe” Falls -- 1:20,000 Fires -- 1:50,000 Poisoning -- 1:40,000 Total -- 1:10,000 Radiation (1 mSv) is safe 1:20,000 Deaths per population – annual 1 mSv = 100 mrem 10CFR20 annual exposure limit for members of the general public is 100 mrem

Relative Risk: Years of Life Lost HPS Position Statement on Radiation Risk in Perspective

Relative Risk: Days of Life Lost

Relative Risk: Hours of Life Lost Anti-nuclear activists Government

Summary of Ionizing Radiation Effects All radiation may not be harmful However, data does not contradict the linear, non-threshold theory for some effects (cancer, genetic effects) Effects from high doses are known fairly well Depending upon dose, radiation may affect various cells, tissues, and organs Without medical treatment, about 50% of people exposed to approximately 450 rad of radiation are expected to die within 1-2 months Acute (short-term) effects below 100 rad are relatively minor

Summary of Ionizing Radiation Effects Effects from low doses occur less frequently and take longer to develop than high dose effects Studies of populations chronically exposed to low levels of radiation have not shown conclusive evidence of increased cancer risk The magnitude of the risk is inferred from data at higher doses The lower the dose of radiation, the longer it takes for the cancer to develop Some changes in blood have been detected down to several rad International Agency for Research on Cancer (IARC) – US cohort of nuclear power plant workers – low levels of ionizing radiation chronic exposure

Summary of Ionizing Radiation Effects Genetic effects have not been detected in people Genetic effects may occur, but at rates so low that they have not been detected over the rate that occurs in the absence of radiation The unborn child and young children appear to be more sensitive to the effects of radiation than adults are The rate that effects occur is very low

The End Questions or Comments?

References 1. Casarett, A.P., Radiation Biology, Prentice Hall, Inc., Englewood Cliffs, NJ, 1968. 2. Cember, Herman, Introduction to Health Physics, 3rd. Ed., McGraw-Hill, New York, NY, 1996. 3. Gollnick, Daniel A., Basic Radiation Protection Technology, 3rd Ed., Pacific Radiation Corporation, Altadena, CA, 1994. 4. International Commission on Radiological Protection (ICRP), 1990 Recommendations of the ICRP, Report #60, Pergamon Press, Elmsford, NY, 1991. 5. International Commission on Radiological Protection (ICRP), Risks Associated with Ionizing Radiations; Annals of the ICRP, Volume 22, No. 1, Pergamon Press, Elmsford, NY, 1991. 6. Moe, H. J., Operational Health Physics Training, ANL-88-26 Corrected, United States Department of Energy, 1992. 7. National Academy of Sciences/National Research Council (NAS/NRC), Health effects of exposure to low levels of ionizing radiation: BEIR V; Washington, D.C., National Academy Press, 1990. 8. National Council on Radiation Protection and Measurements, NCRP Report No. 93, Radiation Exposure of the Population of the United States, Washington, D.C., 1987.

For More Information on Radiation Protection HEALTH PHYSICS SOCIETY 1313 DOLLEY MADISON BLVD., SUITE 402 MCLEAN, VA 22101 (703) 790-1745 WEBSITE: http://www.hps.org CARL TARANTINO, CHP DOMINION GENERATION (804) 273-3068 E-MAIL: carl.tarantino@dom.com