Radiobiology Flashcards
Radiobiology definition
The study of the effects of ionizing radiation on living systems
What are the 2 results of radiology on the chemistry at the cellular level
- Direct effect
- Energy passed directly to biologic molecule
- Can damage DNA in cell
- Indirect effect
- Energy absorbed by water in organism cells, and water is ionized
- Which leads to another effect
Direct Effects
4
- X rays interact with bilogic molecules by removing a hydrogen atom and an electron in the creation of free radicals
- Free radicals are highly to other molecules, are short lived
- Free radicals may lead to dissociations and cross-linking of the DNA
- Both of which result in altered form and function of molecules
- About 1/3 of biologic effects on organisms are the consequence of direct effects
Indirect Effects
- Radiolysis of water producing organic free radicals
- Complex series of chemical changes involved
- Leads to formation of
- Peroxide (H2O2)
- Peroxyl (HO2*) radicals
- These are both primary toxins produced by ionizing radiation
- 2/3 of biologic damage comes from indirect effects
How long do direct and indirect effects take to happen and to manifest
Both take 10^5 seconds to happen, years to manifest
DNA changes
Lead to 4
- Interaction with DNA is the primary source of cell death, genetic mutations and carcinogenesis
- Breakages
- Cross-linking to other DNA or proteins
- Change or loss of base
- Disruption of the hydrogen bonds between DNA strands
DNA Strand Breakage
4
- Single or double strand breaks
- Singe breaks are readily repairable using the second strand as a template
- Double strand breaks are responsible for most cell killing, carcinognesis and heritable effects
- Only need one photon to cause all of this mayhem!!!!!
Effects of Cells
3
- Nucleus is the most radiosensitive part of the cell
- Cell cycle sensitivity
- Mitosis and G2>G1>S
- G2 is most sensitive bc editing is complete
- S is leasat sensitive bc there is proofreading actively occuring
- Chromatid and chromosome aberrations
Radiation Genetics
2 Factors
- Dose
- Frequency of mutations increase in proportion to dose
- Mutations are usually deleterious to organism
- IE Loss of form and function, not new function
- Frequency of mutations increase in proportion to dose
- Differnt tissues have differnet sensitivities to radiation
- Rapidly dividing cells
- Longest mitotic potential
- Undifferentiated cells
- All of these are more radiosensitive
Law of Bergonie and Tribondeau
- High radisensitivity
- Bone marrow, spleen, lymph nodes, gonads, lymphocytes
- Medium radiosensitivity
- Skin, organs (liver, heart, lungs)
- Low radiosensitivity
- Muscle, bone, NS
Tissue and Organ Effects
Deterministic Vs Stochastic Effects
- Deterministic
- Effects that occur that depend on dose absorbed
- Effects occur once the threshold is reached
- Caused by killing of many cells
- High radiation WILL lead to symptoms
- Stochastic Effect
- Effects occur independent of dose
- No thershold
- Caused by sublethal damage to DNA
- Probability, like smoking–> inc prob but one may never get cancer
List Example, caused by, Threshold dose, Severity of effect and dose, Probability of having effect and dose for Deteministic and stochastic
- Dterministic Stochastic
- Ex:
- XRT Mucositis Cataracts / Radiation induced cancer
- Caused by
- Killing of many cells / Sublethal damage to DNA
- Threshold dose
- Yes / No
- Severity of effect and dose
- Greater the dose greater the effect / all or none response, independent of dose
- Probability of having effect and dose
- All indivisuls show effect above thershold / Greater the dose, greater the probability of fx
Tissue and Organ Effects
- Loss of large numbers of cells results in observable result
- Levels much higher than diagnostic imaging
- Levels related to therapy levels
Radiation Therapy (XRT)
**Pathoology
- Squamous cell carcinoma is the most common cancer affecting oral cavity
- Treated with resection unless advanced, invasive or inaccesible then XRT is used
*
Short term effects
- Days to weeks after exposure
- Effects are noted as a decrease in radiosensitive cells: hair, mucosa, bone marrow, lymphocytes