Re: DNA breaks

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

>What are the references to data that demonstrate ionizing
>radiation causes DNA strand breaks?  Is this idea only an >hypothesis, or 
>are there experimental data that conclusively >demonstrate the idea is 
>true?

Here are a few DNA strand break references:
Ahnstrom G. Review of techniques for measuring DNA single-strand breaks. 
Published around 1989 in Int. J. Radiat. Biol.
Cedervall B. et al., Methods for the quantification of DNA double-strand 
breaks determined from the distribution of DNA fragment sizes measured by 
pulsed field gel electrophoresis. Radiat. Res. Vol. 143, 1995:8-16. The 
paper evaluates different mathematical approaches. For those interested – 
please note that the most important figure (2c) was published in the October 
issue (Vol. 144, p.122) – the publisher lost the figure for some reason – my 
proof reading copy was OK so that was not the problem (there was no reason 
to put it on an errata page - we didn't submit anything erroneous to them - 
there is a new publisher now BTW).
Cedervall B and Radivoyevitch T., Methods for analysis of DNA fragment 
distributions on pulsed field gel electrophoresis gels. Electrophoresis, 
Vol. 17, 1996:1080-1086. This paper reviews several methods for breaks that 
are approximately randomly distributed. We also included 3-4 new 
mathematical methods. In a second paper (TR & BC, Mathematical analysis…, 
Vol. 17, 1987-93) we also corrected some earlier equations for unbroken 
chromosomes.
G. Iliakis, The role of DNA double-strand breaks in ionizing 
radiation-induced killing of eukaryotic cells, BioEssays, Vol. 13, 
1991:641-648. This paper is a nice and easy reading summarizing the 
association between DSBs, chromosomal aberrations and cell killing.
Lange C.S., Cole A. and Ostashevsky J.Y., Radiation-Induced damage in 
chromosomal DNA molecules: Deduction of chromosomal organization…, Adv. 
Radiat. Biol., Vol. 17, 1993:261-421.
Lett J. T., Damage to DNA and chromatin structure from ionizing radiations, 
and the radiosensitivity of mammalian cells. Progr. Nucleic Acid Res. Mol. 
Biol., Vol. 32, 1990:305-352.
My thesis (ISBN 91-628-1688-8, 1995) on DSBs (lots of references) was sent 
to many radiation biology departments etc worldwide – and may not have 
decayed completely yet.
For molecular biology update and reviews on DSBs – some good information can 
be found in Radiat. Res. 1998 (Supplement to the November issue). More 
reviews have been published after that. If anyone is interested in recent 
papers on DNA-PKcs, ATM etc I can come back to that.

The DNA breaks and their repair was discovered in the 1960:ies. Many 
published - non-methodological papers deal with DNA DSBs & radiosensitivity 
of mammalian cell lines or yeast. There is still a lot to do in the field of 
specific chromosomal aberrations and its relation to the function of the 
DNA-PKcs, RAD52 group, ATM related protein products. This includes analysis 
of the DSB repair kinetics. A nice challenge regarding the order (zero, 
first, second) of the repair kinetics was recently published in Radiat. Res. 
- it is good that someone brought up this point since most workers seem to 
assume first order reactions without questioning why. This topic is 
important for those who wish to understand the molecular biology functions 
from a mechanistic point. If the math is wrong the descriptions will never 
become consistent between labs, cell lines, laboratory run conditions etc 
and good data may seem more chaotic than necessary.