Lecture 21 - Fetal Radiation Effects & Cataractogenesis

ONCOL 335 - Radiobiology. University of Alberta

What is embryogenesis

Embryogenesis is the process by which the embryo forms and develops from fertilization to the formation of critical structures and organ systems

what part of development does embryogenesis cover?

the first 8 weeks

what is the term for the embryo after 9 weeks

fetus

what is a fetus

a prenatal human between the embryonic state and it’s birth

• implies that the embryo has developed to to a stage of being recognizable as a human, with the development of major organs and body systems.

3 radiation effects on embryo/fetus

• lethal effects

• malformations

• growth disturbances/retardation

what do radiation effects to embryo/fetus depend on?

• dose

• dose rate

• stage of gestation when irradiated

when are lethal effects (prenatal/neonatal deaths) most common

in the early stages of pregnancy: before or immediatly after implantation

after implantation, do you need more or less dose to cause lethality

more

when are embryo malformations most common

during organogenesis, between weeks 3 and 8 of gestation

when are growth disturbances/retardation most common

can happen at all stages, but particulary later in pregnancy

what is the average human gestation period?

40 weeks / 280 days

what animals do humans have a similar gestation period to?

cattle and bison

what two animals have the longest gestation period

• elephants (22 months)

• deep sea octopus (4.5 years)

gestation period of mice

19-21 days

gestation period of rats

20-22 days

what is pre-implantation

fertilization w/o attachment to uterus wall

what radiation effect is most common in mice during pre-implantation period after 2 Gy

prenatal death

what is organogenesis

period of major organ formation (after implantation)

what two radiation effects are most common in mice during organogenesis period after 2 Gy

1. abnormalities (most common)

2. neonatal death

do genetic malformations occur in rats during the pre-implantation stage?

no

what two reasons explain why we dont see malformations in rats when irradiated in pre-implantation period

1. embryo does not make it to term

2. embryo survives as it recovers during organogenesis

in both mice and rats, what is the most radiosensitive period of pregnancy

pre-implantation

does growth retardation and abnormalities occur in radiated pre-implantation

no

• either death or survival without malformations.

when will a mouse/rat survive irradiation in the pre-implantation period

if the radiation only damages a few cells as cell division will make up for it

• if too many cells affected = death

what is the threshold dose to cause embryonic death in pre-implantation period

100 mGy

what dose causes 100% incidence of congenital anomalies in mice and rats in the organogenesis period

• mice = 1 Gy

• rats = 2 Gy

what congential anomalies occur in organogenesis period

growth retardation

what is the least radiosensitive period in mouse/rat gestation?

fetal period

• high doses needed for effects

where did we get the data for radiation effects on embryo/fetus in humans?

from atomic bomb survivors

if the bomb went off and the embryo was <4 weeks old, would babies come to term?

no

prenatal death would occur

Did birth defects occur in embryos <15 weeks when bomb went off?

no

• all or nothing effect

three most common effects to embryos who survived till birth

1. growth retardation

2. mental retardation

3. microcephaly

all later effects

what gestational stage does microcephaly occur

seen in gestational weeks less than 16 weeks

what gestational stage does mental retardation occur

between 8-15 weeks

what doses were required for mental retardation and severe mental retardation

normal = 0.1 Gy

severe = 0.3 Gy

list three other defects associated with radiation to human fetus

1. childhood cancer

2. cataracts

3. spina bifida

stochastic effects require damage to a_____ cell

a single cell

deterministic (threshold) effects require damage to ____

multiple cells

• severity increases with dose

generally, at what dose do consequences to human embryos and fetuses occur

0.1 Gy

What are cataracts

a clouding of the lens of the eye that decreases visions

symptoms of cataracts

faded colors, blurry vision, halos around light, trouble seeing in bright or dark environments

what causes radiation induced cataracts

irradiation to transparent lens fibres causes clouding

why are cataracts deterministic effects?

the more radiation = more fibres damaged = more clouding

describe the surgery to remove cataracts

ultrasound probe breaks lens and removes it, then a fake lens is put in

when do cataracts normally form

in old age

• irradiation speeds up the formation of them

what type of radiation is strong at inducing cataracts

neutrons

where do cataracts most commonly form

the posterior portion of the eye

if a person receives a dose of 2.5-6.5 Gy, how long will it take for cataracts to form

8 years

if a person receives a dose of 6.5-11.5 Gy, how long will it take for cataracts to form

4 years

how is the opasity of cataracts measure

with a scheimpflug imaging system

how does a scheimpflug imaging system diagnose cataracts

system captures high-resolution, cross-sectional images of the anterior segment of the eye by using an angled camera and slit-beam illumination to assess lens opacity and diagnose cataracts objectively.

what is the threshold dose for getting cataracts?

2 Gy

• threshold deterministic effect