How Does Radiation Trigger Genetic Mutations?

[Andrew Mason]

There is a general belief that radiation can cause genetic mutation. I have never understood the mechanism by which such mutation could result.

An alpha particle (+helium nucleus), beta particle (-electron) or a gamma ray (high energy em radiation with a wavelength smaller than an atomic diameter) whizzing through a strand of DNA could obviously break some chemical bonds and knock out some atoms. But it is not going to substitute one nucleic acid (each with a molecular weight of about 500) for another and change the genetic code. The effect will be a random rearrangement of some of the constitutent atoms, not a change in the genetic code.

I conclude that radiation alone cannot physically cause genetic mutation. If it causes mutation it must do so by triggering some biological process that results in mutation. So what is the biological mechanism by which radiation is supposed to cause genetic mutation?

AM

 

[Monique]

It is ionizing radiation that is dangerous, as you say it can break chemical bonds and knock out electrons out of their orbits, or neutrons can physically collide with an atom.

Ionizing radiation can have a direct effect on DNA, by causing single or double strand breaks, or it can have an indirect effect when free radicals (produced by the ionizing radiation) attack and modify the bases.

 

[Andrew Mason]

It is ionizing radiation that is dangerous, as you say it can break chemical bonds and knock out electrons out of their orbits, or neutrons can physically collide with an atom.

Ionizing radiation can have a direct effect on DNA, by causing single or double strand breaks, or it can have an indirect effect when free radicals (produced by the ionizing radiation) attack and modify the bases.

That is a perfectly good explanation of how radiation can cause DNA damage. But my question is: how does it cause genetic mutation? Does a mutation not require some rearrangment of the ACGT sequence of nucleic acids in the DNA molecule - and doesn't the mutation have to occur exactly the same way on both strands? Is a damaged DNA molecule all that is needed to cause a mutation that can be passed on to successive generations?

Ionizing radiation can knock off some hydrogen atoms or perhaps (by neutron capture) induce atomic nuclei to become radioactive and decay. But the probability that radiation can rearrange DNA by itself has to be virtually nil. It has been my impression that the information redundancy within the DNA molecule and the ease with which DNA damage can be detected within the cell (ie. loss of double helix structure) are important reasons that DNA has evolved as the basis for all cellular life.

AM

 

[Rade]

See these links:
http://taylorandfrancis.metapress.c...,247,535;linkingpublicationresults,1:100668,1
http://mcb.asm.org/cgi/content/abstract/14/3/1901
http://www.rerf.or.jp/eigo/radefx/basickno/radcell.htm
http://en.wikipedia.org/wiki/DNA_repair
http://enhs.umn.edu/hazards/hazardssite/radon/radonmolaction.html
Also, not all natural mutations of DNA are repaired--most but not all. Over time these mutations add up, can cause problems with cell division (cancer). External radiation can only quicken this process. Clearly, radiation alone does cause genetic mutation, the experimental evidence is conclusive. Do not confuse this fact with arguments of radiation hormesis (helpful aspects of radiation)--see these:
http://interactive.snm.org/docs/Radiation_Hormesis_JNMT_March_O3.pdf
http://interactive.snm.org/index.cfm?PageID=5159&RPID=10

 

[Monique]

I can explain it further, let me first clarify some more how often you can expect a certain DNA damage per Gy (taken from lecture notes of the Netherlands Cancer Institutes):

30 interstrand crosslinks
40 double strand breaks (most lethal type of damage)
150 DNA-protein crosslinks
500-1000 single strand breaks
1000-2000 base damages

* Base damage (oxidized, methylated, missing bases) and single strand breaks are repaired by the base excition repair pathway, that takes out damaged bases and fills in the the gap by matching the bases with the complementary strand.
* Double strand breaks are repaired by homologous recombination, non-homologous end-joining (most common) and single strand annealing.
* Crosslinks (pyrimidine dimers, protein adducts) are repaired by nucleotide excision repair and homologous recombination.
* Mismatched bases are repaired by mismatch repair.

So how does a DNA break or base damage cause genetic mutation, especially with all the repair mechanisms in place.

Sometimes a base is modified in such a way that it looks a lot like another base. During DNA replication the DNA polymerase will integrate the wrong base and so a mutation is fixed.

DNA breaks are not clean, there are usually several nucleotides damaged. Repair can go faulty. Also, non-homologous recombination is a quick-fix for repairing double-strand breaks, but often deletions or additions occur. Homologous recombination is much more accurate, but it is a slow process since the damaged DNA needs to find its homolog.

So radiation does not rearrange DNA, but it damages it in such a way that during repair or replication wrong bases are put in.

 

[Andrew Mason]

So radiation does not rearrange DNA, but it damages it in such a way that during repair or replication wrong bases are put in.

Thank-you for a very helpful reply. I will feed on that for a while and see where it takes me.

AM

 

[Andrew Mason]

See these links:
http://taylorandfrancis.metapress.c...,247,535;linkingpublicationresults,1:100668,1
http://mcb.asm.org/cgi/content/abstract/14/3/1901
http://www.rerf.or.jp/eigo/radefx/basickno/radcell.htm
http://en.wikipedia.org/wiki/DNA_repair
http://enhs.umn.edu/hazards/hazardssite/radon/radonmolaction.html
Also, not all natural mutations of DNA are repaired--most but not all. Over time these mutations add up, can cause problems with cell division (cancer). External radiation can only quicken this process. Clearly, radiation alone does cause genetic mutation, the experimental evidence is conclusive. Do not confuse this fact with arguments of radiation hormesis (helpful aspects of radiation)--see these:
http://interactive.snm.org/docs/Radiation_Hormesis_JNMT_March_O3.pdf
http://interactive.snm.org/index.cfm?PageID=5159&RPID=10

Thanks for the links, which I have read now.

I have another thread on Hormesis https://www.physicsforums.com/showthread.php?t=148847"

It is the hormetic effect that intrigues me. The cell repair mechanisms may be stimulated by being 'exercised' by having to repair radiation damage. There doesn't seem to be a lot of research on the actual mechanism by which this might occur.

Alternatively, it occurs to me that radiation may stimulate the immune system to detect and remove damaged cells that the cell repair mechanisms cannot fix. It is not clear (to me at any rate) what the hormetic effect results from.

AM