Re: DNA damage from low-LET radiation

["Drew Thatcher" <Thatcher.Drew@home.com>]

Andy - my additions are provided after your individual questions.  I'll
admit that you seem to always be asking probing questions.  I'm responding
to all in the spirit of keeping this discussion alive.

Cheers,
Drew Thatcher, MSHP, CHP
thatcher.drew@home.com
360.236.3255

-----Original Message-----
From: Karam, Andrew <Andrew_Karam@URMC.Rochester.edu>
To: Multiple recipients of list <radsafe@romulus.ehs.uiuc.edu>
Date: Friday, April 16, 1999 1:48 PM
Subject: DNA damage from low-LET radiation


>I recently read a letter by John Wards in Radiation Research (1991)
>discussing qualitative differences in DNA damage caused by radiation as
>opposed to other mutagens. It sounds as though he is saying that even
>low-LET radiation causes DSBs, which is contrary to what I had always
heard.
>This suggests to me that the difference in radiation "quality", then, would
>stem from the number of DSBs a particular radiation causes.

I believe this is a true statement Andy.  SSBs from low dose low LET
radiation, assuming a sufficiently low enough dose rate to prevent multiple
track hits within the same area of interest, are quickly and efficiently
repaired.  DSBs are therefore important in causing chromosomal damage and
biological effects.

Is anyone>familiar with this letter or the underlying research?  Would it be
accurate
>to say that all radiations cause DSBs, but that high-LET radiations have a
>higher probability of causing them in any particular cell, accounting for
>the higher RBE of alpha and neutron radiation?

Sorry, I'm not familiar with this article.  Yes, those are true statements
and can be estimated using models such as the Theory of Dual Radiation
Action.

 Also, is it still safe to say>that much damage from low-LET radiation is
indirect, caused by free radical>formation within the cell and that this
process is enhanced by the>occasional DSB?

Yes, most damage from low LET radiation is indirect (Primer of Medical
Radiobiology - E. LaTorre Travis) due primarily to the large amount of water
available within a cell and the correspondingly small volume of DNA.  Both
direct and indirect radiation cause single strand breaks.   If the dose/dose
rate is sufficiently high enough, then the possibility exists for multiple
desposition events within a given target volume (as a result of inter and
intra track events) to result in DSBs.  So, perhaps it would be more
accurate to say that free radical formation enhances the possibility of
DSBs.  The 2 deposition events (or SSBs if indirect effects are included)
would have to be located within 20-30 nm (about 20 base pairs).  the timing
of these indirect effects is critically important  - notes from Dr. Chris
Wang - GT.

Can anyone suggest to me further reading that might help to
>better explain this to me?

Perform a QUEST search for Dr. Harold Rossi (Columbia University).  He has
published numerous articles, many of which are directly relevant to your
question.  Obtain a copy of ICRU 39  (38?) and 40.  They are a discussion of
lineal energy transfer as a more appropriate method by which to measure
radiation damage.  ICRU 40 describes Dual radiation action theory - this
model enables one to estimate probabilities of multiple hits within cells
(hence the greater possibility of DSBs).

Other papers of interest:

Charlton, D.E. and Humm, J.L., A method of calculating initial DNA strand
breakage following the decay of incorporated I-125.  Int. J. Radiat. Biol.,
Vol. 53 (3) 353-365, 1988.

Radford, I.R., The level of induced DNA double strand breakage correlates
with cell killing after X irradiation,  Int. J. Radiat. Biol. 48 (1) 45-54,
1985.

>This interests me for the following reasons:
>It seems contrary to what I understood to be conventional wisdom regarding
>the nature of damage from low-LET radiation
>If there is a qualitative difference between damage due to low-LET
radiation
>and other mutagens, this suggests to me that there may be similarly
>qualitative differences between mechanisms to repair radiation damage as
>compared to other DNA damage.

I seem to recall that biological damage from radiation is no different from
other types of damage - hence no unique effects from radiation.  That being
true, then it would stand to reason that other non radioactive impacts
presumably create similar possibilities for SSB and DSB - particularly since
the formation of free radicals would or should be similar.

>I would greatly appreciate any information or references anyone may care to
>offer.  Thanks!
>Andy
>P. Andrew Karam, CHP
>Radiation Safety Officer
>University of Rochester
>(716) 275-1473 (voice)
>(716) 256-0365 (fax)
>andrew_karam@urmc.rochester.edu
>
>There is no Chase so pleasant, methinks, as to drive a Thought, by good
>conduct, from one end of the World to the other; and never to lose sight of
>it till it fall into Eternity, where all things are lost as to our
>knowledge.    T. Burnet, The Theory of the Earth, 1697
>
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