Radiation Biology: Embryologic and Genetic Effects

GSD stands for:

Genetically Significant Dose

what is GSD

a concept used to assess the impact of gonadal dose

the 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

what is the concept of GSD suggesting

that genetic consequences of the substantial absorbed doses of gonadal radiation became significantly less when averaged over an entire population rather than applied to just a few of its members

How much more exposure do female organs receive during an exam involving the pelvic region than do males

3x

when used properly, flat contact shields reduce gonadal exposure by ___

50%

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

90-95%

what is DNA

Sugar phosphate side rails joined by nitrogenous bases

ionizing radiation on DNA can cause:

Single strand breaks-point lesions

Double strand breaks- widely spaced or cleaved chromosomes

Cause mutations

Ionizing radiation on chromosomes:

Chromosome breaks, fragments, anomalies (aberrations)

the period of gestation during which the embryo-fetus is exposed to radiation governs the effects

Genetic/ hereditary effects

Stages of gestation in order

Preimplantation→organogenesis→fetal

period of gestation that corresponds to approx. 10 days to 12 weeks after conception

Organogenesis

why are cells extremely radiosensitive during organogenesis

because the embryonic cells begin to divide and differentiating after conception

when is the most crucial period with respect to harmful consequences

1st trimester

why is the 1st trimester the most crucial period for harmful effects

during this time the nerve cells in the brain and spinal cord of the fetus are most susceptible to radiation induced congenital abnormality

within two weeks of fertilization if a high dose is received by the embryo, what is the most adverse effect

Prenatal death presenting as a spontaneous abortion

In doses of ___ mSv within the first 12 weeks, what is usually a result of the radiation

200mSv, usually resulting in death or severe congenital abnormalities

during pre implantation, (0-9 days), a dose of ___-___ Gyt will cause embryologic death

0.05-0.15 Gyt

At what stage do malformations not occur

Pre-implantation

exposure during organogenesis can cause:

Growth inhibition

Intellectual disability

microcephaly

Genital deformities

Sense organ damage

Leukemia

during what stage does the presence of nonminor abnormalities cause neonatal death

late-organogenesis

when does skeletal damage occur most often

During the period from the 3rd to the 20th week of development

other possible functional effects of irradiation during the fetal stage

Cancer and functional disorders

leukemia can be induced by exposure during what stages

most sensitive during 1st trimester but can happen during 2nd and 3rd as well

approx. ___% of all live births in the US have some type of abnormality

4%

why can abnormalities caused by radiation be very hard to estimate

because human genes can vary naturally

3 general effects on the embryo fetus

1. Lethality

2. Congenital abnormalities present at birth

3. Long term effects or effects not visible at birth but develop later

Defined as the biological effects of ionizing radiation on future generations, are a result of radiation induced damage to the DNA molecule in sperm or ova

Genetic (Hereditary) effects

Defined as the changes in genes caused by the loss or change of a base in the DNA chain, permanent change that provides an altered set of instructions for some cellular function

Mutation

Defined as mutations that occur at random without known cause, they are natural phenomenon

Spontaneous mutations

are spontaneous mutations permanent and hereditary?

yes

some examples of spontaneous mutations

Hemophilia

Huntingtons chorea

Down syndrome

Duchennes muscular dystrophy

Sickle cell anemia

Cystic fibrosis

Hydrocephalus

mutation frequency:

a certain number of spontaneous mutations arising each generation as part of the natural order of events

some hereditary disorder is present in __% of all live births in US

10%

Agents that can increase the frequency of mutations

1. Ionizing radiation

2. Viruses

3. Chemicals

Defined as the radiation dose that causes the number of spontaneous mutations occurring in a given population to double

Doubling dose

The doubling dose in humans is estimated at ____ Sv

1.56 Sv

radiation produces mutations through un repaired structural breaks in the DNA called _______

point mutations

point mutations can be either _____ or ______

dominant or recessive

mutation that will probably be expressed in the offspring

Dominant

Mutation that will probably not be expressed for several generations

recessive

radiation causes what kind of mutations

Recessive

for a recessive mutation to appear in the offspring, ______ parent must have the same genetic effect

Both

why is shielding so important in terms of mutations

An increase in the number of individuals who receive radiation exposure raises the likelihood that 2 individuals with the same type of mutation will have children

recessive mutations may manifest itself in subtle changes such as:

Allergies, slight alterations in in metabolism, pre disposition to certain diseases

where does the only evidence of ionizing radiation causing damage come from

Experimentation on fruit flies and mice

what did H.J Mueller prove in 1927 while experimenting with fruit flies

He proved that any dose of radiation, however small, to germ cells results in some form of genetic risk

*hereditary effects do not have a threshold

what did Dr. Russel in 1946 prove when experimenting with white mice

That frequency of radiation induced mutations is directly proportional to the dose received

*hereditary effects are linear