BIOLOGICAL BIOLOGICAL EFFECTS EFFECTS

OF OF RADIATIONRADIATION

WILLIAM CROOKES

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Crookes Tube

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WILHELM CONRAD ROENTGEN

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Mrs. Roentgen’s

hand

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Early radiograp

h

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Dr. Kassabian in his

Philadelphia lab

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Dr. Kassabian’s hands

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Thomas Alva Edison

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Clarence Dally

Edison’s assistant

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Direct EffectsDirect EffectsDirect EffectsDirect Effects

Direct interaction with DNADirect interaction with DNA

++

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Hydrolysis of WaterHydrolysis of WaterHydrolysis of WaterHydrolysis of Water

Radiation ionizes Radiation ionizes a water moleculea water molecule

The ion reacts The ion reacts with another with another water molecule water molecule to form the to form the highly reactive highly reactive hydroxyl radicalhydroxyl radical

HH22OO HH22OO+ + + e + e--

HH22OO+ + + H+ H22OO HH33OO+ + + OH + OH

Indirect Effect

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DNA

“Target Molecule”

POSSIBLE EFFECTS OF POSSIBLE EFFECTS OF RADIATIONRADIATION

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

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The Law of Bergonié and The Law of Bergonié and TribondeauTribondeau

This law states…This law states… Stem cells are radiosensitive; Stem cells are radiosensitive;

mature cells are radioresistant.mature cells are radioresistant. Younger tissues and organs are Younger tissues and organs are

radiosensitive.radiosensitive. Tissues with high metabolic Tissues with high metabolic

activity are radiosensitive.activity are radiosensitive. A high growth rate for tissues A high growth rate for tissues

result in increased radiosensitivity.result in increased radiosensitivity.

The following tissue types are The following tissue types are radiosensitive:radiosensitive:

GerminalGerminal…reproductive cells of the ovary …reproductive cells of the ovary and testisand testis

HematopoieticHematopoietic (blood forming) tissues… (blood forming) tissues…red bone marrow, spleen, lymph nodes red bone marrow, spleen, lymph nodes and thymusand thymus

Intestinal crypt cellsIntestinal crypt cells – cells on the – cells on the surface of the intestinesurface of the intestine

The The leastleast radiosensitive radiosensitive would be tissue such as:would be tissue such as:

MuscleMuscle

NerveNerve

EARLY EFFECTSEARLY EFFECTS

VS.VS.

LATE EFFECTSLATE EFFECTS

EARLY EFFECTSEARLY EFFECTS

(Prompt Effects)(Prompt Effects)

After a high, single radiation After a high, single radiation exposure in a short period of exposure in a short period of

timetime

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Non-Stochastic Health Non-Stochastic Health EffectsEffects

Acute effects are Acute effects are “Non-stochastic”“Non-stochastic” effects effects

The effects become The effects become more severe as more severe as the exposure increases. the exposure increases.

In other words, In other words, the amount of the the amount of the dosedose does not determine the does not determine the probability of the effect, it probability of the effect, it determines the severity of the determines the severity of the effecteffect..

ACUTE RADIATION ACUTE RADIATION SYNDROMESYNDROME

Prodromal Stage

Latent Period

Manifest Illness Stage

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ACUTE RADIATION ACUTE RADIATION SYNDROMESSYNDROMES

Hematologic Syndrome

Gastrointestinal Syndrome

Central Nervous System Syndrome

Hematologic SyndromeHematologic Syndrome

200 – 1,000 Rad200 – 1,000 Rad

Prodromal Stage:Prodromal Stage: Mild symptoms appear Mild symptoms appear within a few hours and last for several within a few hours and last for several daysdays

Latent Period: Latent Period: May last up to 4 weeksMay last up to 4 weeks Manifest Illness: Manifest Illness: Vomiting, diarrhea, Vomiting, diarrhea,

fatigue and fever – Decline in blood cells – fatigue and fever – Decline in blood cells – Recovery in 2 to 4 weeks…May last up to Recovery in 2 to 4 weeks…May last up to 6 months 6 months

Possible deathPossible death due to infection, due to infection, dehydration or hemorrhagedehydration or hemorrhage

Gastrointestinal Gastrointestinal SyndromeSyndrome

1,000 – 5,000 Rad1,000 – 5,000 Rad

Prodromal Stage: Prodromal Stage: Vomiting and Vomiting and diarrhea occur within hours and last up diarrhea occur within hours and last up to one dayto one day

Latent Period: Latent Period: Lasts 3-5 daysLasts 3-5 days Manifest Illness: Manifest Illness: Nausea, vomiting Nausea, vomiting

and diarrhea – Worsens to bloody stools and diarrhea – Worsens to bloody stools DeathDeath within 4 to 10 days after within 4 to 10 days after

exposure primarily due to intestinal cell exposure primarily due to intestinal cell damage – Also damage to blood-forming damage – Also damage to blood-forming tissue results in hemorrhaging and tissue results in hemorrhaging and dehydration.dehydration.

Central Nervous System Central Nervous System SyndromeSyndrome

Greater than 5,000 RadGreater than 5,000 Rad

Prodromal Stage: Prodromal Stage: Severe nausea and vomiting Severe nausea and vomiting within a few minutes – Nervousness, confusion, within a few minutes – Nervousness, confusion, burning skin, vision loss…possible loss of burning skin, vision loss…possible loss of consciousnessconsciousness

Latent Period: Latent Period: May last up to 12 hours, or not May last up to 12 hours, or not at allat all

Manifest Illness: Manifest Illness: Disorientation, loss of muscle Disorientation, loss of muscle control, breathing problems, seizures, comacontrol, breathing problems, seizures, coma

DeathDeath always within a few days of exposure – always within a few days of exposure – due to increased fluid in brain (pressure) – due to increased fluid in brain (pressure) – Death occurs before hematologic and Death occurs before hematologic and gastrointestinal symptoms appeargastrointestinal symptoms appear

LD 50/60LD 50/60

The dose of radiation to the The dose of radiation to the whole whole bodybody that will result in death within that will result in death within 60 days60 days to to 50%50% of the subjects of the subjects receiving the dosereceiving the dose…if no treatment …if no treatment is givenis given

For humans…approximately 350 radFor humans…approximately 350 rad People have survived up to 850 rad People have survived up to 850 rad

if treatment is receivedif treatment is received

OTHER OTHER EARLY EFFECTSEARLY EFFECTS

(Lower doses or localized)(Lower doses or localized)

SKIN

GONADS

BLOOD COUNT REDUCTION

CELLULAR CHROMOSOME DAMAGE

SKIN EXPOSURESKIN EXPOSURE

ERYTHEMAERYTHEMA Threshold approximately 200 radThreshold approximately 200 rad SED50 approximately 600 radSED50 approximately 600 rad

ULCERATIONULCERATION At higher dosesAt higher doses

EPILATIONEPILATION Localized hair lossLocalized hair loss

ANGIOPLASTY ANGIOPLASTY EXPOSUREEXPOSURE

Photographs courtesy of Thomas B. Shope, Ph.D. (FDA)

6-8 WEEKS AFTER

3RD ANGIOPLASTY

5 MONTHS LATER 22 MONTHS LATER

OVARIES AND TESTES OVARIES AND TESTES EXPOSUREEXPOSURE

200 rad – Temporary sterility200 rad – Temporary sterility 500 rad – Permanent sterility500 rad – Permanent sterility 10 rad – Possible genetic mutation 10 rad – Possible genetic mutation

(testes)(testes) 25-50 rad – Possible genetic 25-50 rad – Possible genetic

mutation (ovaries)mutation (ovaries)

HEMATOLOGIC HEMATOLOGIC EFFECTSEFFECTS

A dose as low A dose as low as about 25 as about 25 rad may cause rad may cause a reduction in a reduction in blood cell blood cell countscounts

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CYTOGENETIC EFFECTSCYTOGENETIC EFFECTS

Doses as low as 5 rad may cause some Doses as low as 5 rad may cause some cellular chromosome aberrationscellular chromosome aberrations

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LATE EFFECTSLATE EFFECTS

After an acute exposure or an After an acute exposure or an extended chronic exposureextended chronic exposure

Take months to years to Take months to years to become evidentbecome evident

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Stochastic Health EffectsStochastic Health Effects

Late effects are Late effects are “Stochastic”“Stochastic” effects effects The effects become The effects become more probable more probable

as the exposure increases. as the exposure increases. In other words, In other words, the amount of the the amount of the

dose dose determines the determines the probability of probability of the effectthe effect, it does not determine the , it does not determine the severity of the effect.severity of the effect.

Late EffectsLate Effects

CataractsCataracts Cancer (including leukemia)Cancer (including leukemia) Mental retardation (fetal Mental retardation (fetal

doses)doses)

LATE EFFECTSLATE EFFECTSRISK ESTIMATESRISK ESTIMATES

Difficult to quantifyDifficult to quantifyEpidemiological studies Epidemiological studies neededneeded

A-BOMB SURVIVORSA-BOMB SURVIVORS

Hiroshima

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A-BOMB SURVIVORSA-BOMB SURVIVORS

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Hiroshima & NagasakiHiroshima & Nagasaki•300,000 total population300,000 total population

•100,000 killed100,000 killed

•100,000 survivors with 100,000 survivors with significant radiation dosessignificant radiation doses

•Increased leukemia Increased leukemia occurrenceoccurrence

•Increased mental Increased mental retardation (8-15 weeks retardation (8-15 weeks gestation)gestation)

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MARSHALL ISLANDSMARSHALL ISLANDS

•1940’s & 1950’s

•Nuclear Testing Fallout

•Thyroid Cancer data

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EARLY RADIOLOGISTSEARLY RADIOLOGISTS

Increased occurrence of leukemia and other effects

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ANKYLOSING ANKYLOSING SPONDYLITIS PATIENTSSPONDYLITIS PATIENTS

•1940’s and 1950”s

•Arthritic spine condition

•100 – 4,000 rad

•Permanent cure

•Increased occurrence of leukemiaImage from: http://hcd2.bupa.co.uk/images/factsheets/ankspond.gif

RADIUM DIAL RADIUM DIAL PAINTERSPAINTERS

•1920’s and 1930’s

•Dose of up to 50,000 rad to the bone

•Increased occurrence of bone cancer

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URANIUM MINERSURANIUM MINERS

•Radon exposure

•Increased occurrence of lung cancer

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RISK MODELSRISK MODELSImage from: http://bfa.sdsu.edu/ehs/doseresponse.gif

RISK MODELRISK MODELLinear Non-thresholdLinear Non-threshold

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CANCER RISK CANCER RISK ESTIMATESESTIMATES

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

ALARAALARA

Assuming linear non-threshold modelAssuming linear non-threshold model

All radiation exposure poses some riskAll radiation exposure poses some risk

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PREGNANCY RISKPREGNANCY RISK1st trimester has most

risk

Possible effects:

1.Death

2.Congenital abnormalities

3.Cancer induction

4.Growth impairment

5.Mental retardation

6.Genetic effectsImage from:http://www.diabetesuffolk.com/Managing Diabetes/Planning a pregnancy.asp

Effects of 10 Rad in Effects of 10 Rad in UteroUtero

TimeTime ResponseResponse Nat Nat OccurOccur

Rad Rad ResponseResponse

Up to 2 Up to 2 wkswks

Spont Spont abortionabortion

25%25% 0.1%0.1%

2-10 wks2-10 wks CongenitalCongenital 5%5% 1%1%

2-15 wks2-15 wks Mental ret.Mental ret. 6%6% 0.5%0.5%

Up to 9 Up to 9 mosmos

CancerCancer 8/10,0008/10,000 12/10,00012/10,000

Up to 9 Up to 9 mosmos

Impaired Impaired dev.dev.

1%1% 00

Up to 9 Up to 9 mosmos

Gen Gen MutationMutation

10%10% 00Radiologic Science for Technologists, 7th edition, Stewart C. Bushong, (pg. 512)

REMEMBER…

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