Radiation Genetics

1. Radiation Effects on DNA

2. Radiation Effects on chromosomes

- Change or loss of a base (Mutation)

- Single Strand Break

- Double-Strand Break

- Double-Strand Break in the same Rung of DNA

- Covalent Cross-Links

It destroys the triplet code and may not be reversible

The direct consequence of this damage is an alteration of the base sequence

It may cause acute consequences for the cell but more important, if the cell remains viable, incorrect genetic information will be transferred to one of the two daughter cells when the cell divides

can be repaired easily, because the opposite strand serves as a template

The ionization of a DNA macromolecule resulting in a break of one of its chemical bonds

thereby severing one of the sugar-phosphate chain side rails or stands of the ladderlike DNA molecular structure

This type of injury (Single Strand Break) to DNA is called a

The ionization of a DNA macromolecule that results in the rupture of one or more of its chemical bonds

thereby creating one or more breaks in each of the two sugar-phosphate chains of the DNA ladderlike molecular structure

It is not fixed as easily as single- strand breaks

Double-Strand Break is also called?

can sever the DNA molecule, making repair, difficult, because the opposite strand template is lost

ladderlike molecule structure (A) causes complete chromosome breakage, resulting in a cleaved or broken chromosome (B)

The result is a cleaved or broken chromosome, with each new portion containing an unequal amount of genetic

material

If this damaged chromosome divides, each new daughter cell will receive an incorrect amount of genetic material.

This will culminate in either death or impaired functioning of the new daughter cell

Interstrand covalent cross-link produced by high-energy radiation acting directly on a DNA molecule

Chemical unions created between atoms by the single sharing of one or more pairs of electrons

Directly initiated by high-energy radiation.

At low energies, however, are probably caused by the process of indirect action

1. Intrastrand cross-link

2. Interstrand cross-link

3. DNA molecules also may become covalently linked to a protein molecule

a cross-link that form between two places on the same DNA strand

It happen between complementary DNA strands or between entirely different DNA molecules

DNA molecules also may become covalently linked to a

3 Principal observable effects that may result from irradiation of DNA

During the __ portion of interphase, the chromosomes replicate form a two-chromatid structure (A) to a four-chromatid (B)

While the __ phase is taking place, two sister chromatids like the one shown in (A) join to become a chromosome (B). A centromere links them together

1. One arm of one chromosome - restitution

2. One Arm of Two Chromosomes - Acentric chromosome, Dicentric chromosome, Translocation

- Restitution

- rejoining and healing of the broken ends of the chromosome

- No damage to cell

Single Break Effect

One Arm of Two Chromosomes

- Acentric chromosome

- Dicentric chromosome

- Translocation

It is the joining of 2 chromatids without a centromere

It is the joining of two chromatids with centromeres.

It is the joining of acentric fragment from one chromosome to the fragment containing the centromere of the other chromosome.

Normal appearing chromosome but there is a change in its gene sequence.

is sometimes associated with translocation of chromosomes. At its simplest, translocation occurs when a portion of one chromosome switches position with another chromosome

- one arm of one chromosome: deletion, inversion

- both arms of one chromosome: acentric chromosome, inversion, ring chromosome

Double Break Effect

- deletion

- inversion

Chromosome appears normal, contain original number of genes and DNA, however the sequence of bases has been altered

process wherein the fragments between the break is deleted

Deleted fragments is lost during cell division

The acentric fragment will join with the fragment with centromere form a normal looking chromosome but lacking in genetic material

the fragment with broken ends turn around and rejoin thereby reversing its position on the chromosome.

Double Break Effect

a. Acentric chromosome

b. Inversion

c. Ring chromosome

results when broken ends of the fragment with the centromere moves about and twist before joining

- Interphase Death

- Mitotic (Genetic) Death

- Mitotic Delay

- Reproductive Failure

- Interference with function

Apoptosis, programmed cell death

Cell death before entering mitosis

A nonmitotic, or non-division, form of cell death that occurs when cells die without attempting division during the interphase portion of the cell life cycle.

Occurs spontaneously in both normal tissue and in tumors

The more radiosensitive the cell is, the smaller the dose required to cause apoptotic death during interphase

A few hundred centigray (cGy) can kill very sensitive cells such as lymphocytes or spermatogonia

For less radiosensitive cells, such as those in bone, apoptosis may require radiation doses of several thousand cGy

Occurs when a cell dies after one or more divisions

Even relatively small doses of radiation can cause this type of cell death

The radiation dose required to produce __ __ is less than the dose needed to produce apoptosis in slowly dividing cells or nondividing cells

The failure of the cell to start dividing on time

Exposing a cell to as little as 0.01 Gy of ionizing radiation just before it begins dividing can cause this

After this delay the cell may resume its normal mitotic function

The underlying cause of this phenomenon is not known

Generally results from exposure of cells to doses of ionizing radiation in the range of 1 to 10 Gy.

The cell does not die, it permanently loses its ability to procreate but continues to metabolize and also to synthesize nucleic acids and proteins

The termination of the cell's reproductive abilities does, however, prevent the transmission of damage to future generations of cells.

Permanent or temporary interference with cellular function independent of the cell's ability to divide can be brought about by exposure to ionizing radiation

If repair enzymes are able to fix the damage, the cell can recover and continue to function

- Somatic Effects

- Genetic Effects

The effects develop in an exposed individual.

- Short Term

- Long Term

- Stochastic (probabilistic) effects

- Non-probabilistic (deterministic) effects

Also referred to as the statistical response

Increasing the dose increases the probability of damage, but the severity of the effect is independent of the dose

This may cause cancer induction and genetic effects

Governed by probability

It is formerly called non-stochastic effect

It is thought to be threshold, as there are doses below which the effect is not observe

The examples are radiation burns, cataracts, erythema, fibrosis, and hematopoietic damage

The increase in severity with dose, and thus are considered to be threshold

The effects of radiation on the embryo and fetus depend on the stage of development and the radiation dose.