Re: DSBs

["Bjorn Cedervall" <bcradsafers@hotmail.com>]

>Does this mean that there is a qualitative
>difference between DSB's caused by high-LET, low-LET radiations and
>non-radiation events?  If so, would each of these types of DSBs have a 
>different probability of repair?  Or would some be more likely lethal than
>others?  I just assumed that all DSBs were pretty much the same.

A human somatic cell has probably at least 2 to 4 different ways(I would 
say, with present knowledge typicallly 3 different ways) of repairing what 
we may measure as DSBs depending on cell cycle context, complexity of the 
lesion, and also depending on cell type (lymphocytes probably lack at least 
one mode of DSB repair). The high-LET lesions may even be double DSBs and it 
is possible that whole DSB loops (hundreds of kbp) can be lost as large 
deletions. In a mix of cells those which are apoptotic may have very 
different DSB break pattern (non Poisson distributed) as compared to other 
cells. If one measures DSBs in a mix of cells, several different classes of 
DNA fragment distributions may be superimposed and difficult to analyze. All 
these issues are still partly subject to investigations and the normal 
enzymatic machinery for repair probably needs 1-2 more decades of research 
before we really understand it well. Some hints about mechanisms can be 
found by looking at distributions of different chromosome aberrations within 
a cell and between cells. Then there is the topic of interaction (for 
instance during DNA repair) between chemically induced lesions/breaks and 
radiation induced breaks (part of my present work with a few collaborators).

And finally we have the subtopic repair/misrepair (often the word 
"rejoining" is better to use). It is probably normal that mammalian cells 
misrepair a lot of DSBs and still survive. All these events I have mentioned 
are subject to different probabilities that depend on a number of physical, 
chemical (like thiol metabolism), and biological factors.

My own ideas - not necessarily coinciding with those of others,

Bjorn Cedervall   bcradsafers@hotmail.com

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