BIOLOGICAL EFFECTS OF RADIATION

WILLIAM CROOKES Image from:

Crookes Tube Image from:

WILHELM CONRAD ROENTGEN Image from:

Mrs. Roentgen’s hand Image from:

Early radiograph Image from:

Dr. Kassabian in his Philadelphia lab Image from:

Dr. Kassabian’s hands Image from:

Thomas Alva Edison Image from:

Clarence Dally Edison’s assistant Image from:

Direct Effects Direct interaction with DNA + Image from:

Hydrolysis of Water Radiation ionizes a water molecule Radiation ionizes a water molecule The ion reacts with another water molecule to form the highly reactive hydroxyl radical The ion reacts with another water molecule to form the highly reactive hydroxyl radical H2OH2OH2OH2O H 2 O + + e - H 2 O + + H 2 O H 3 O + + OH Indirect Effect Image from:

DNA “Target Molecule”

POSSIBLE EFFECTS OF RADIATION 1.Radiation may pass through cell without doing any damage. 2.Damage may occur, but be repaired. 3.The damaged cell may reproduce itself in its damaged form. 4.The cell may die. DAMAGE CAN BE REPAIRED Image from:

The Law of Bergonié and Tribondeau This law states… Stem cells are radiosensitive; mature cells are radioresistant. Stem cells are radiosensitive; mature cells are radioresistant. Younger tissues and organs are radiosensitive. Younger tissues and organs are radiosensitive. Tissues with high metabolic activity are radiosensitive. Tissues with high metabolic activity are radiosensitive. A high growth rate for tissues result in increased radiosensitivity. A high growth rate for tissues result in increased radiosensitivity.

The following tissue types are radiosensitive: Germinal…reproductive cells of the ovary and testis Germinal…reproductive cells of the ovary and testis Hematopoietic (blood forming) tissues…red bone marrow, spleen, lymph nodes and thymus Hematopoietic (blood forming) tissues…red bone marrow, spleen, lymph nodes and thymus Intestinal crypt cells – cells on the surface of the intestine Intestinal crypt cells – cells on the surface of the intestine

The least radiosensitive would be tissue such as: Muscle Muscle Nerve Nerve

EARLY EFFECTS VS. LATE EFFECTS

EARLY EFFECTS (Prompt Effects) After a high, single radiation exposure in a short period of time Image from:

Non-Stochastic Health Effects Acute effects are “Non-stochastic” effects Acute effects are “Non-stochastic” effects The effects become more severe as the exposure increases. The effects become more severe as the exposure increases. In other words, the amount of the dose does not determine the probability of the effect, it determines the severity of the effect. In other words, the amount of the dose does not determine the probability of the effect, it determines the severity of the effect.

ACUTE RADIATION SYNDROME Prodromal Stage Latent Period Manifest Illness Stage Images from:

ACUTE RADIATION SYNDROMES  Hematologic Syndrome  Gastrointestinal Syndrome  Central Nervous System Syndrome

Hematologic Syndrome 200 – 1,000 Rad Prodromal Stage: Mild symptoms appear within a few hours and last for several days Prodromal Stage: Mild symptoms appear within a few hours and last for several days Latent Period: May last up to 4 weeks 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 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 Possible death due to infection, dehydration or hemorrhage

Gastrointestinal Syndrome 1,000 – 5,000 Rad Prodromal Stage: Vomiting and diarrhea occur within hours and last up to one day Prodromal Stage: Vomiting and diarrhea occur within hours and last up to one day Latent Period: Lasts 3-5 days Latent Period: Lasts 3-5 days Manifest Illness: Nausea, vomiting and diarrhea – Worsens to bloody stools 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. 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.

Central Nervous System Syndrome Greater than 5,000 Rad Prodromal Stage: Severe nausea and vomiting within a few minutes – Nervousness, confusion, burning skin, vision loss…possible loss of consciousness 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 Latent Period: May last up to 12 hours, or not at all Manifest Illness: Disorientation, loss of muscle control, breathing problems, seizures, coma Manifest Illness: Disorientation, loss of muscle control, breathing problems, seizures, coma Death always within a few days of exposure – due to increased fluid in brain (pressure) – Death occurs before hematologic and gastrointestinal symptoms appear Death always within a few days of exposure – due to increased fluid in brain (pressure) – Death occurs before hematologic and gastrointestinal symptoms appear

LD 50/60 The dose of radiation to the whole body that will result in death within 60 days to 50% of the subjects receiving the dose…if no treatment is given The dose of radiation to the whole body that will result in death within 60 days to 50% of the subjects receiving the dose…if no treatment is given For humans…approximately 350 rad For humans…approximately 350 rad People have survived up to 850 rad if treatment is received People have survived up to 850 rad if treatment is received

OTHER EARLY EFFECTS (Lower doses or localized)  SKIN  GONADS  BLOOD COUNT REDUCTION  CELLULAR CHROMOSOME DAMAGE

SKIN EXPOSURE ERYTHEMA ERYTHEMA Threshold approximately 200 rad Threshold approximately 200 rad SED50 approximately 600 rad SED50 approximately 600 rad ULCERATION ULCERATION At higher doses At higher doses EPILATION EPILATION Localized hair loss Localized hair loss

ANGIOPLASTY EXPOSURE Photographs courtesy of Thomas B. Shope, Ph.D. (FDA) 6-8 WEEKS AFTER 3 RD ANGIOPLASTY 5 MONTHS LATER 22 MONTHS LATER

OVARIES AND TESTES EXPOSURE 200 rad – Temporary sterility 200 rad – Temporary sterility 500 rad – Permanent sterility 500 rad – Permanent sterility 10 rad – Possible genetic mutation (testes) 10 rad – Possible genetic mutation (testes) rad – Possible genetic mutation (ovaries) rad – Possible genetic mutation (ovaries)

HEMATOLOGIC EFFECTS A dose as low as about 25 rad may cause a reduction in blood cell counts A dose as low as about 25 rad may cause a reduction in blood cell counts Image from:

CYTOGENETIC EFFECTS Doses as low as 5 rad may cause some cellular chromosome aberrations Doses as low as 5 rad may cause some cellular chromosome aberrations Image from:

LATE EFFECTS After an acute exposure or an extended chronic exposure Take months to years to become evident Image from:

Stochastic Health Effects Late effects are “Stochastic” effects Late effects are “Stochastic” effects The effects become more probable as the exposure increases. The effects become more probable as the exposure increases. In other words, the amount of the dose determines the probability of the effect, it does not determine the severity of the effect. In other words, the amount of the dose determines the probability of the effect, it does not determine the severity of the effect.

Late Effects Cataracts Cataracts Cancer (including leukemia) Cancer (including leukemia) Mental retardation (fetal doses) Mental retardation (fetal doses)

LATE EFFECTS RISK ESTIMATES Difficult to quantify Difficult to quantify Epidemiological studies needed Epidemiological studies needed

A-BOMB SURVIVORS Hiroshima Image from:

A-BOMB SURVIVORS Image from:

Hiroshima & Nagasaki 300,000 total population300,000 total population 100,000 killed100,000 killed 100,000 survivors with significant radiation doses100,000 survivors with significant radiation doses Increased leukemia occurrenceIncreased leukemia occurrence Increased mental retardation (8-15 weeks gestation)Increased mental retardation (8-15 weeks gestation) Image from:

MARSHALL ISLANDS 1940’s & 1950’s Nuclear Testing Fallout Thyroid Cancer data Image from:

EARLY RADIOLOGISTS Increased occurrence of leukemia and other effects Image from:

ANKYLOSING SPONDYLITIS PATIENTS 1940’s and 1950”s Arthritic spine condition 100 – 4,000 rad Permanent cure Increased occurrence of leukemia Image from:

RADIUM DIAL PAINTERS 1920’s and 1930’s Dose of up to 50,000 rad to the bone Increased occurrence of bone cancer Image from:

URANIUM MINERS Radon exposure Increased occurrence of lung cancer Image from:

RISK MODELS Image from:

RISK MODEL Linear Non-threshold Image from:

CANCER RISK ESTIMATES ONE MILLION PEOPLE EXPOSED TO 1 RAD 50 to 150 deaths from radiation induced cancer occurring within 25 years 100,000 PEOPLE EXPOSED TO 100mrad/YEAR 19,000 would die from cancer without exposure Increased cancer deaths estimated at about 550

ALARA Assuming linear non-threshold model All radiation exposure poses some risk Image from:

PREGNANCY RISK 1 st trimester has most risk Possible effects: 1.Death 2.Congenital abnormalities 3.Cancer induction 4.Growth impairment 5.Mental retardation 6.Genetic effects Image from: Diabetes/Planning a pregnancy.asphttp:// Diabetes/Planning a pregnancy.asp

Effects of 10 Rad in Utero TimeResponse Nat Occur Rad Response Up to 2 wks Spont abortion 25%0.1% 2-10 wks Congenital5%1% 2-15 wks Mental ret. 6%0.5% Up to 9 mos Cancer8/10,00012/10,000 Impaired dev. 1%0 Up to 9 mos Gen Mutation 10%0 Radiologic Science for Technologists, 7 th edition, Stewart C. Bushong, (pg. 512)

REMEMBER… Radiation does not produce unusual genetic mutations…it can only increase the frequency of mutations normally observed.