Embryologic and Genetic Effects (3/4/2025)

What does GSD stand for?

genetically significant dose

Explain genetically significant dose (GSD)

• a concept used to assess the impact of gonadal dose

• GSD is the equivalent dose (EqD) to the reproductive organs that, if received by every human, would be expected to bring about an identical gross genetic injury to the total population

• suggests that genetic consequences of the substantial absorbed doses of gonadal radiation become significantly less when averaged over an entire population rather than just a few members

What does GSD stand for?

genetically significant dose

Explain genetically significant dose (GSD)

• a concept used to assess the impact of gonadal dose

• GSD is the equivalent dose (EqD) to the reproductive organs that, if received by every human, would be expected to bring about an identical gross genetic injury to the total population

• suggests that genetic consequences of the substantial absorbed doses of gonadal radiation become significantly less when averaged over an entire population rather than just a few members

The US Public Health Services estimates the GSD for the population of the U.S. to be approximately ___

0.20 mSv

Explain gonadal shielding

using a shield protects the reproductive organs from exposure but it is a secondary protective measure

Female organs receive ___ more exposure during radiographic procedures involving the pelvic region than do male organs

3x

Flat contact shields (when properly placed) reduce gonadal exposure by ___

50%

Primary beam can be reduced by ___ for males when the contact shield is used

90-95%

What are the side rails and rungs of the DNA ladder?

side rails: sugar phosphate bonds

rungs: nitrogenous bases (A, T, C, G)

Ionizing radiation causing a single strand break is called ___

point lesion

Ionizing radiation causing a double strand break is called ___

cleaved chromosomes or widely spaced chromosomes

Ionizing radiation on DNA can cause:

• single strand breaks

• double strand breaks

• mutations

Ionizing radiation on chromosomes can cause:

• chromosome breaks

• fragments

• anomalies/aberrations

Genetic/hereditary effects are caused when ___

the embryo-fetus is exposed to radiation

When is organogenesis?

the period of gestation that corresponds to approximately 10 days to 12 weeks after conception

Why are embryonic cells extremely radiosensitive during the organogenesis period?

the cells begin dividing and differentiating after conception

The ___ trimester seems to be the most crucial period with respect to harmful consequences

1st

If a high dose of radiation is received by the embryo within ___, prenatal death is the most obvious adverse effect

within 2 weeks of fertilization (before the start of organogenesis)

(if death does not occur, the pregnancy will continue to term without any negative effect)

___ presents as spontaneous abortion

prenatal death

Irradiation of the embryo-fetus during the first 12 weeks of development in doses higher than ___ frequently results in death or severe congenital abnormalities

200 mSv (20 rem)

When is the pre-implantation stage?

0-9 days after conception

During the pre-implantation stage, a dose of ___ will cause embryologic death

0.05 to 0.15 Gy_t

Do malformations occur during the pre-implantation stage?

NO

Exposure during organogenesis can cause:

• growth inhibition

• intellectual disability

• microcephaly

• genital deformities

• sense organ damage (sight, sound, smell)

• leukemia

During late organogenesis, the presence of nonminor abnormalities will cause ___

neonatal death (death at birth)

Skeletal damage occurs frequently during the period of ___ of development (usually in the early part of the window)

3rd to the 20th week

(in the late part of the window, neurologic anomalies are more common)

Fetal radiosensitivity ___ as the gestation progresses

decreases

The risk of radiation induced leukemia is greatest in the ___ trimester, but can be induced in the other trimesters as well

1st

Can the effects of low-level ionizing radiation be estimated?

can only be poorly estimated

Approximately ___ of all live births in the U.S. have some type of abnormality

4%

What are 3 general effects on the embryo-fetus?

1. lethality

2. congenital abnormalities present at birth

3. long-term effects (childhood malignancy), or effects not visible at birth but develop later

Define and explain genetic (hereditary) effects

• the biological effects of ionizing radiation on future generations

• occur as a result of radiation-induced damage to the DNA molecule in the sperm or ova, leading to germ cell alterations

Define mutation

• a change in genes caused by the loss or change of a base in the DNA chain

• a permanent change that provides an altered set of instructions for some cellular function

What are spontaneous mutations?

• mutations that occur as random (without known cause)

• a natural phenomenon

• these mutations are permanent and hereditary; passed form generation to generation

• a certain number occur in each generation (mutation frequency)

What are some examples of spontaneous mutations?

• hemophilia

• Huntington’s chorea

• down syndrome

• Duchenne’s muscular dystrophy

• sickle cell anemia

• cystic fibrosis

• hydrocephalus

Define mutation frequency

the number of spontaneous mutations that arise in each generation as part of the natural order of events

Some hereditary disorder is present in approximately ___% of all live births in the US

___% of these are harmul

10% of births; 99% are harmful

What are 3 agents that can increase the frequency of mutations?

• ionizing radiation

• viruses

• chemicals

Define doubling dose (and what is it in humans?)

• the radiation dose that causes the number of spontaneous mutation occurring in a given population to double

• doubling dose in humans is estimated at 1.56 Sv

What unique congenital abnormalities does radiation induce?

radiation induces no unique congenital abnormalities

Radiation produces mutations through unrepaired structural breaks in the DNA called ___

point mutations

Point mutations may be either ___ or ___

dominant or recessive

A ___ mutation will probably be expressed in the offspring

dominant

A ___ mutation will probably not be expressed for several generations

recessive

Radiation causes ___ mutations

recessive

For a recessive mutation to appear in the offspring, ___

both parents MUST have the same genetic defect

Damage from recessive mutations sometimes manifests in subtle changes commonly related to ___

metabolism or immune system (allergies, slight metabolic alterations, predisposition to certain diseases)

H. J. Mueller 1927 experiment

• fruit flies

• proved that any dose of radiation to germ cells results in some form of genetic risk

• proved that hereditary effects do not have a threshold

Dr. Russell 1946 experiment

• white mice

• proved that the frequency of radiation induced mutations is directly proportional to the dose received

• proved that hereditary effects are linear

2001 UNSCEAR study on genetic effects of radiation

concluded that no radiation-induced inherited disease has so far been demonstrated in human populations exposed to ionizing radiation

(it is still recommended to avoid irradiation of gonadal tissue)