Radiation Biology 5 --- Late Effects, Malignancy, & Pregnancy

late effects is not observed for ____________________ after exposure

6 months/more

___________ cases of radiation induced skin cancer w/in 15yrs of discovery of x-rays

100

Patient & Rad Tech doses are considered _____________________ & are typically ___________ (high or low) dose & LET

1. fractionated
2. low

most late effects are __________________ effects

stochastic (probabilistic)

Late non-stochastic somatic effects are directly related to ____________ _____________________ & occur months to years after high radiation exposure & have a threshold

dose received

Late non-stochastic (deterministic) effects have a __________________, while late stochastic (probabilistic) effects do not have a _______________________.

threshold

late deterministic effects

1. cataracts
2. fibrosis
3. organ atrophy
4. reduced fertility/sterility

late probabilistic effects

1. cancer
2. leukemia
3. fetus in utero

late effects can remain ___________________ & produce damage in a person's offspring

dormant

somatic effects impact the ___________________________, while genetic effects impact the ___________________________.

1. individual
2. offspring

Somatic effects

experienced by exposed individual (erythema, epilaition, cataracts)

Genetic effects

irradiation of reproductive cells & transmitted to next generation

Dx XR is considered (3)

1. low dose
2. low LET
3. chronic (delivered over periods of time)

late effects of low dose

1. Radiation induced malignancy
2. Genetic effects
3. Life span shortening
4. Local tissue effects

observable harm

-sufficient # of cells have been lost & loss of tissue function
-Probability is 0 at low doses, probability & severity ↑ w/ ↑ dose
-Seen in individual

Most late effects follow ______________ _______________ dose response

linear non-threshold

somatic cells exposed

-probability of cancer ↑ w/ dose (no threshold)
-severity of cancer not dose related (stochastic)
-"all or nothing" effect (get it or you don't)

epidemiology

study of distribution & cause of disease in human populations

epidemiology is an observable science of collecting info from humans & is used to determine:

late effects

why is it difficult to determine late effects to radiation?

1. Frequency of response to radiation is low
2. Dose is presumed low & unknown
3. Dose cannot be 100% connected to radiation exposure

risk estimates

calculated to determine risk of something occurring (i.e. cancer)

3 types of risk estimates

1. relative risk
2. excess risk
3. attributable risk

relative risk

Calculated by comparing # of people in exposed population showing stochastic effect w/ # of those who show same effect in unexposed population

relative risk formula

observed cases/expected cases

relative risk values

1 = no risk
1.5 = frequency 50% higher in irradiated groups

relative risk for radiation induced effects observed in humans

1-2

radiation hormesis

Theory that low radiation may be beneficial (

excess risk

-incidence of disease in irradiated populations exceeds the expected
-Difference btwn observed # & expected #

excess risk formula

observed cases - expected cases

attributable risk

Predicts that excess radiation induced cancer is constant for life

late skin effects are often seen in which layer of skin?

dermis

Telangiectasia

dilated superficial blood vessels

Irradiation of blood-forming organs can cause ______________________ _______________________ (early) or ___________________ (late)

1. hematologic depression
2. leukemia

T/F: lymphocyte damage can be early & late response

true

cataracts

opacity of eye lens that occurs due to aging, trauma, metabolic disease, etc.

where do radiation induced cataracts occur in the eye?

posterior pole of lens

T/F: lens of the eye does not undergo cell division, which causes cataracts

false

radiosensitivity of the eye is ______ dependent

age
-older = higher effect & shorter latent period

cataracts follow ____________________ dose response curve

non-linear threshold

Dose of > _____ Gy will cause cataracts in almost all irradiated

10 Gy

threshold dose for acute exposure cataracts

2 Gy

As dose ____________________, latent period ______________.

-increases
-decreases

4 long term somatic effects

1. Cancer
2. Genetic effects/embryologic damage
3. Life span shortening
4. Local tissue effects (cataracts)

T/F: rad techs today have significant life span shortening

false

according to BUSHONG, what is the worst expected is reduced life span for rad techs?

~10 days for every 10 mGy

latent period

time btwn irradiation & appearance of malignancy

latent period for leukemia

4-7 years

latent period for solid tumors

10-60 years

at-risk period

period where radiation effect is expected to occur

Radiation-Induced Malignancy follows a ___________________ _____________________________ dose response curve & is considered _________________________________.

-linear non-threshold
-stochastic

what malignancy is best established risk linked to radiation exposure?

leukemia

increased risk for leukemia

1. atomic bomb survivors
2. earlys rads
3. ankylosing spondylitis patients
4. children irradiated in utero

A-bomb survivors have a relative risk of ________ & incidence in >_______x expected

-2.77
-100

At risk period for radiation induced leukemia is ___________________.

lifetime

early rads received >1 Gy/year & had high incidence of leukemia due to:

little/no radiation protection

what was used to treat ankylosing spondylitis pts in the 1940-50s?

radiation

T/F: Irradiation in utero shows ↑ risk for leukemia

true

T/F: thyroid cancer is 4x higher in females than males

true

thyroid is more sensitive is kids & has a latent period of:

10-20 years

Radiation tx of benign breast diseases (postpartrum mastitis dose .75-10 Gy) caused this disease

breast cancer

50% miners in germany & colorado died from exposure to ________________, that causes lung cancer

Radon

relative risk of lung cancer for miners

8:1

relative risk for miners that smoked

20:1

skin cancer has a latent period of _________________________ & follows a _____________________ dose response

- 5-10 years
-threshold

skin cancer in RTs started as _______________________, and progressed to malignancy

radiodermatitis

why was incidence of skin cancer so high in early days of radiation?

-low kVp XRs
-rad therapy w/ orthovoltage
-little/no protection

thoratrast was a contrast agent from 1925-1945 & contained _____________________, which is an alpha, beta, & gamma emitter

thorium

thorium could cause cancer in these organs

-liver
-spleen
-angiosarcomas
-biliary duct carcinomas

latent period for liver cancer

15-20 years

Radium girls ingested this element while working in watch factories

radium

radium 226 half life

1620 years

radium 228 half life

6 years

Ra deposited in done & caused many diseases, including:

-osteoporosis
-osteogenic sarcoma
-epithelial carcinoma of nasopharynx & paranasal sinuses

radium salts were also used to treat these 3 conditions:

1. ankylosing spodylitis
2. arthritis
3. TB

more complex species =

more radiosensitive

T/F: · Low dose chronic radiation impairs fertility

false

irradiation before pregnancy

interrupted fertility

irradiation during pregnancy

possible congenital effects

irradiation post pregnancy

suspected genetic effects

Factors of Importance for biologic damage from irradiation

1. Stage of gestation (time-related)
2. Dose to fetus

Irradiation in utero may cause (7):

1. Prenatal death (before birth)
2. Neonatal death (@ birth - 28 days)
3. Congenital abnormalities
4. Malignancy induction
5. Growth impairment
6. Intellectual disability
7. Genetic effects

which trimester is most radiosensitive?

first trimester

T/F: radiation was once used to induce therapeutic abortions

true

stages of developement

1. pre-implantation
2. major organogenesis
3. fetal/growth

pre-implantation

-conception to 10 days
-Cells undifferentiated
-Fertilization until attachment to uterine wall

major organogenesis

-10 days to 8th week
-cells implanted in uterine wall
-Cells differentiate into organs

fetal/growth stage

-9 weeks to end of pregnancy
-structures grow & develop

W/in 2 weeks of fertilization, most common effect is _____________________ _________________, or failure to implant, which is likely @ ↑ doses

prenatal death (spontaneous abortion)

why is the pre-implantation period considered "all or nothing"?

cells are either killed or fix damages thru divisions

Dose of _____________ during first 2 weeks will result in .1% rate of spontaneous abortion

100mGy (.1 Gy)

first 2 weeks are of least concern due to

all or nothing response

major organogenesis is the most sensitive period due to

organ & bone formation

effects during organogenesis

-Skeletal/organ abnormalities
-Congenital abnormalities of CNS
-Malignant disease (leukemia)
-Prenatal death

dose of ______________ during organogenesis will ↑ incidence of congenital abnormalities by about 1%

100 mGy

intellectual disability effects are __________ dependent, as well as stage of development

dose

irradiated Week 8 - 25:

noted ↓ in IQ scores

irradiated Before 8/after 25:

IQ changes not observed

intellectual disability from irradiated is of most concern during ________________, when brain cells of the cerebrum are proliferating

8-15 weeks

Dose of ____________ expected to ↑ normal incidence of intellectual disability by .5%

100 mGy

microcephaly

small head; does not mean intellectual disability