Can Intense X-Rays Cause Non-Stochastic Damage to Biological Structures?

[EinsteinKreuz]

I'd like to know some specifics about the biological effects of X-rays on living tissue. I am aware that X-rays, along with other forms of ionizing radiation, have stochastic effects of DNA but what is the data regarding the non-stochastic effects of intense X-rays? In particular, can sufficient intense X-rays cause non-stochastic damage to ribosomes as well as proteins? Are there uses for intense X-rays in radiosurgery? And moreover does the dosage of focused X-rays required to kill specific tissue masses by fragmenting biological macromolecules depend of the specific frequency and do broadband X-rays have more cytotoxic efficacy than monochromatic X-rays with a specific frequency(not to mention absorption of certain X-ray frequencies by ribosomes).

 

[Simon Bridge]

"Sufficiently intense" x-rays can punch holes in things ... I'm afraid you'll need to be more specific.
X-rays are among the most studied of ionizing radiation so there is a great deal of data.
The followup questions you have posed are all searchable online, i.e.

Effect of x-rays on ribosomes:
http://www.sciencedirect.com/science/article/pii/0006300263905791

X-rays in radiosurgury:
http://www.hopkinsmedicine.org/healthlibrary/conditions/radiology/radiosurgery_85,P08476/

The best way to use PF is to look stuff up yourself and then ask us about the bits you don't understand.

 

[EinsteinKreuz]

"Sufficiently intense" x-rays can punch holes in things ... I'm afraid you'll need to be more specific.

What I was asking is if the intensity of X-rays required to cause deterministic/non-stochastic biological damage to living cells and tissues is enough to cause radiation burns...Or if X-rays can be used to destroy specific areas of living tissue while leaving the surrounding tissue unharmed and what dosage/timeframe is required to do so.

 

[Simon Bridge]

OK - you were thinking about something specific when you were talking about "damage".
What do you mean by "radiation burns"?

Anything capable of radiation burns (as in sunburn) will also have stochastic effects ... usually around the fringes of the burn volume. However, it is possible to have an x-ray beam that does stochastic damage without burning.
I don't have actual figures - but the actual doses would vary anyway.

 

[EinsteinKreuz]

OK - you were thinking about something specific when you were talking about "damage".
What do you mean by "radiation burns"?

Anything capable of radiation burns (as in sunburn) will also have stochastic effects ... usually around the fringes of the burn volume. However, it is possible to have an x-ray beam that does stochastic damage without burning.
I don't have actual figures - but the actual doses would vary anyway.

When I say "damage" I'm talking about biochemical effects that result in cell death. For example, in the case of ionizing radiation by damage to DNA I would be implying single and double strand breaks caused by X-ray bombardment that results in fragmentation of chromosomes such that the DNA repair enzymes cannot reanneal the strands and transcription can no longer take place. I have read articles about the sterilizing effects of Gamma Rays which result in double strand breaking of DNA that completely fragments the genome and protein synthesis ceases. This is partly caused by the formation of hydroxyl radicals as well as the break of strands by electron ejection.

 

[Doug Huffman]

The field is called health physics and it is well founded and mature.

 

[Simon Bridge]

What I was thinking ... it is possible to look up equivalent papers for double-strand breaking by x-rays.
i.e. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC328056/
... double strand breaks don't have to cause cell death iirc. but the example given does.
I suspect the answers looked for will amount to checking specific mechanisms against "x-ray induced" in the lit.
There's quite a lot on "radiation induced cell death" for example, which includes x-rays.
The short answer remains "there is lots of data".

To narrow it down: what do you need to know for? Context is everything.
But the above should give you a place to start.
Enjoy.

 

[Ygggdrasil]

Ionizing radiation (x-rays, gamma rays) are commonly used in oncology to kill tumor cells. I suspect if you look up a textbook on radiation therapy or radiation oncology, you'd probably be able to find the answers to your questions.

 

[EinsteinKreuz]

Ionizing radiation (x-rays, gamma rays) are commonly used in oncology to kill tumor cells. I suspect if you look up a textbook on radiation therapy or radiation oncology, you'd probably be able to find the answers to your questions.

Yep. I read that article. But it doesn't go into the explicit details of the exact physico-chemical mechanism by which radiation causes cell death. From what I have read about gamma rays, exposure to gamma rays that are >= a threshold intensity level and for a long enough duration will create hydroxyl radicals in addition to genome fragmentation via double strand breaking. So it is my understanding that sufficiently high concentrations of hydroxyl radicals will chemically alter the DNA fragments such that they cannot be re-annealed and transcription stops. In addition there was an article about the effects of gamma ray induced hydroxyl radicals that can degrade E. Coli ribosomes to the point where protein synthesis can no longer occur. Now the effects of ionizing radiation on nucleic acids have been well studied, but if someone can point me to some data about their effects of proteins(particularly DNA repair enzymes) I'm eager to see it. But I haven't found that much about the deleterious effects of X-rays(which can ionize but are lower in energy than gamma rays).

 

[Lok]

Yep. I read that article. But it doesn't go into the explicit details of the exact physico-chemical mechanism by which radiation causes cell death.

There might be more mechanisms to cause cell death. Nucleus DNA fragmentation is not necessarily terminal, and some organelles have their own DNA which can be fragmented by ionizing radiation and this would lead to impaired function too.
Any chemical/macro-molecule present in the cell will be more or less affected by the radiation and whether the cell can go on with what is still functioning is not easily measurable. The hydroxyl radical is not necessarily the only or main culprit.

 

[Astronuc]

Some possible insight - http://www.radiationanswers.org/radiation-introduction/radiation-exposure.html - but short on details.

A little more, but still short on details - http://www.rerf.jp/radefx/basickno_e/radcell.htm

https://www.utoledo.edu/med/depts/radther/pdf/RadbioCh2-3handouts_n.pdf

I believe in addition to hydroxyl radicals, there are peroxyl radicals, which are even more damaging, as well as breaks in the DNA, which if substantial, may be irreparable.

"DNA can be attacked by physical and chemical mutagens. Physical mutagens are primarily radiation sources, including UV (200-300 nm wavelength) radiation from the sun. UV radiation produces covalent bonds that crosslink adjacent pyrimidine (cytosine and thymine) bases in the DNA strand. Ionizing radiation (X-rays) initiates DNA mutations by generating free radicals within the cell that create reactive oxygen species (ROS) and result in single-strand and double-strand breaks in the double helix." Ref: http://www.sigmaaldrich.com/technical-documents/articles/biofiles/dna-damage-and-repair.html

"Moreover, ROS can be generated by radiation (UV, X-rays) . . . It is generally accepted that oxidative stress and ROS eventually cause DNA damage, whereby insufficient cellular repair mechanisms may contribute to premature aging and apoptosis."
from - http://www.ncbi.nlm.nih.gov/pubmed/18208352

http://en.wikipedia.org/wiki/Reactive_oxygen_species
http://en.wikipedia.org/wiki/Reactive_oxygen_species#Oxidative_damage

 

[Choppy]

I don't know if this is a little too late, but I might just add in a few thoughts...

Ionizing radiation (x-rays or gamma rays) will interact with matter through three basic processes: the photo-electric effect, Compton scattering, and pair/triplet production. In soft tissues, the photo-electric effect is dominant for the lower kilovoltage energies, and the Compton effect becomes dominant in the higher kV and megavoltage energies. But the net result it that photons interact and produce electrons that travel through the tissue.

As others have indicated the electrons will travel through cells and generate free radicals and reactive oxygen and nitrogen species. (They can also do direct damage by ionizing critical targets although I believe this is less common.) These then interact with critical targets generating damage.

One thing that's important to understand is that cells are experiencing this kinds of damage all the time. The process of respiration generates reactive oxygen species and these generate damage that your cells have to deal with. Background radiation also contributes to the damage, but from what I understand the background radiation damage is orders of magnitude less than that from other processes. So your cells exist in a steady state of damage and repair all the time.

The next question is what are the critical targets?

There is a lot of evidence to suggest that DNA is the most sensitive structure to this damage. For example you can incorporate Auger-emitting isotopes (they emit electrons with very short ranges) into various different organelles and the cells that have them incorporated into the DNA show the lowest survival and/or clonogenic capacity (the ability to form colonies). DNA is not the only sensitive structure. Mitochondria, for example, are also sensitive to radiation. And given high enough doses of radiation, even cell membranes will begin to break down. Cell "death" can have a number of different meanings. In terms of cancer control, often we're concerned about 'clonogenic death' - stopping the cell from reproducing. But on top of that you can have apotosis, which is a process where the cell detects enough damage that it triggers a set of processes whereby the cell commits suicide in a pre-programmed way. You can also have "necrotic" death, where apoptosis doesn't happen, but enough other processes shut down that he cell simply can't go on to do what it's meant to do - or example being starved on oxygen.

At different incident energies these patterns of energy deposition along the electron tracks will change and the density of ionizations can lead to differences in the effectiveness in the ability of the radiation to kill cells, but when comparing x-Rays with gamma rays the differences are generally small. Dose, or the amount of energy delivered per unit time, is most strongly correlated with effect. There are many other factors that can modify the effectiveness of the delivered dose. These include the amount of oxygen present, the phase of the cell cycle, the repair mechanisms in the cell, and other factors such as the influence of the local environment on the cells' ability to divide (repopulation).