Radiation Effects on DNA Chromosomes and Cells Flashcards
what are the 3 levels of biological damage that can result from exposure to ionizing radiation?
- Molecular (DNA, RNA)
- Cellular (cell structure)
- Organic
what is molecular damage?
structurally changed molecules
What is a chromosome?
- tiny rod-shaped bodies
- composed of protein and DNA
how many chromosomes do a normal human have in somatic cells?
46
how many chromosomes do a normal human have in reproductive (germ) cells?
23
what are the 4 categories of radiation effects on DNA?
- base damage
- single strand breaks
- double strand breaks
- crosslinks or crosslinking
what is base damage?
- change or a loss of a base
- mutation
what are single strand breaks?
- break in the backbone of one chain of a DNA molecule
What are double strand breaks?
- break in both chains of the DNA molecule
What are crosslinks or crosslinking?
- within the DNA molecule (intrastrand) or from one molecule to another (interstrand)
what is a DNA mutation?
- molecular change, not visible in the chromosome
How many feet of DNA in the human body?
How does a single strand break occur?
- Ionizing radiation interacts with DNA macromolecule
- Transfers energy, and ruptures one of the molecule’s chemical bonds possibly severing one of the sugar-phosphate chain side rails
- Repair enzymes are often capable of reversing this damage
How does a double strand break occur?
- Further exposure of the affected DNA macromolecule to ionizing radiation can lead to additional breaks in the sugar-phosphate molecular chain(s).
- Breaks may also be repaired but are not repaired as easily as single-strand breaks.
- If repair does not take place, further separation may occur in the DNA chains, threatening the life of the cell.
- Occur more commonly with densely ionizing (high-LET) radiation.
What happens if there is a double strand break in the same rung of DNA?
- Result is a cleaved or broken chromosome with each new portion containing an unequal amount of genetic material
- If damaged chromosome divides, each new daughter cell will receive an incorrect amount of genetic material culminating in the death or impaired functioning of the new daughter cell.
How do covalent cross-links occur?
- Direct action by high-LET radiation
- Indirect action by low-LET
- Some molecules can fragment or change into small, spurlike molecules that become very interactive (“sticky”) when exposed to radiation, causing these molecules to attach to other macromolecules or to other segments of the same macromolecule chain.
- Can cause reproduction arrest and cell death if not repaired
- Can occur in many different patterns.
where do intrastrand crosslinks occur?
- between two regions of the same DNA strand
where do interstrand crosslinks occur?
between two complimentary DNA strands or completely different DNA molecules
How does mutation occur?
- Interaction of ionizing radiation with a DNA molecule
- Direct consequence is an alteration of the base sequence, a mutation.
- May not be reversible and may cause acute consequences for the cell
- If cell remains viable, incorrect genetic information will be transferred to one of the two daughter cells when the cell divides.
what is a chromosome aberration?
- damage from radiation that occurs before S-phase
- both daughter cells affected
What is a chromatid aberration?
- damage from radiation occurs after S-phase
- only one daughter cell affected
when are cells most sensitive to radiation?
mitosis
When are cells least sensitive to mitosis?
during late S-phase
What are structural changes that can be caused by radiation?
- single break in one chromosome or chromatid
- single break in separate chromosomes or chromatids
- two or more breaks in the same chromosome or chromatid
what is restitution?
- breaks rejoin, no visible damage
- no injury to the cell
- 95% mending/healing
What is deletion?
- fragments lost during mitosis
- after DNA synthesis only part of the chromosome has been replicated
- creates/left with an eccentric fragment (no centromere)
What is broken end rearrangement/distorted chromosomes?
rearrangement of the broken ends
Two breaks in a single chromatid?
- cause a ring chromatid and eccentric fragment
Breaks in two different chromatids?
fragments are separated
Ends of chromatids and ends of fragments join prior to DNA synthesis?
- forming dicentric and acentric fragments
- chromosome is elongated but cannot split
- centromeres are ‘bridged’
- reproductive death of the cell
broken end rearrangement without visible damage to the chromatids?
- translocations and inversions
- genetic material has been rearranged
- drastic change to cell function
- cell death or failure to replicate properly
what are the ways cell nucleus death can reveal itself?
- instant death
- reproductive death
- apoptosis
- mitotic or genetic death
- mitotic delay
- interference with function
- chromosome breakage
what does acentric mean?
no centromere
what does dicentric mean?
2 centromeres
instant death
- high doses of radiation
- DNA breaks up
reproductive death
survives but can’t replicate
apoptosis
programmed cell death (interphase death)
mitotic or genetic death
dies trying to divide
mitotic delay
division delay
effects of irradiation on somatic cells?
If a sufficient quantity of somatic cells are affected, entire body processes may be disrupted.
effects of irradiation on genetic cells
If radiation damages the germ cells, the damage may be passed on to future generations in the form of genetic mutations, mostly recessive.
dose response relationship
mathematical relationship between various radiation dose levels and the magnitude of the observed response
- High levels of x-rays can cause skin burns, cataracts, cancer, leukemia and other harmful effects
- Unknown is the degree of effect after exposure to diagnostic or therapeutic levels of radiation
applications of radiation?
- therapeutic - treating cancers
- radiation protection - estimating biological effects
what is the deterministic effect?
if the radiation response increases in severity with increased radiation dose
what is stochastic effect?
if the radiation response increases in incidence with increased radiation dose
- chances of occurrence increase with additional exposure
what is the dose response relationship in diagnostic radiology?
linear non-threshold
- no exposure is without risk, but small dose has very low risk
