Re: FWD: A technique to measure DNA damage

["Björn Cedervall" <bjorn_cedervall@hotmail.com>]

The paper in Science focuses on thymine glycol which normally is 
produced at a rate of about 2000 lesions per hour in a mammalian cell. 
The cause of this production is mainly oxidative stress which also 
results in the production of at least 20 other base products. Thymine 
glycol and 8-OH-dG constitute about 20-30% of all these. 1 Gy of 
ionizing radiation produces perhaps about 2000 base damages including AP 
sites (base loss sites) and about 1000 single-strand breaks. The thymine 
glycol is produced linearily with dose (ionizing radiation). The 
interest in these lesions due to normal processes is of course their 
extent – even if they are repaired readily – for statistical reasons 
they may occasionally produce more complex damage that may result in 
mutations or other events. LD50 for SSBs (individual cell basis) is in 
the order of 2.5 million simulataneous breaks.

Now, the DSB is generally believed to be the major cause of mutation, 
cell death and carcinogenesis. DSBs also seem to be induced linearily 
with dose. Since thymine glycol is induced linearily with dose – the 
relationship thymine glycol vs. DSBs (for INDUCED breaks – not repaired 
breaks) should also be expected to be linear.

My concern however is the repair phase: A DSB may be of a very complex 
nature and therefore demand a more complex repair machinery (such as 
homologous recombinational repair) as compared to lesions that are more 
limited in their local distribution. The repair systems for these 
respective types of lesions are probably and mainly different.

To me – it is therefore not obvious that these lesions – when it comes 
to consequences such as chromosomal or chromatid aberrations (which in 
turn may lead to mutation, cell death etc) also will follow a linear 
relationship (aberrations caused by complex base lesions vs. aberrations 
caused by direct complex DSBs (including large deletions). This may be a 
reason for much work on DSBs and formed the basis for some hesitation 
from my side.

Sincerely Yours,

Bjorn_cedervall@hotmail.com
Dept. Medical Radiobiology & Medical Radiation Physics,
Karolinska Institutet,
S-171 76 Stockholm, Sweden


>Date: Wed, 3 Jun 1998 10:17:31 -0500 (CDT)
>Reply-To: radsafe@romulus.ehs.uiuc.edu
>From: Bernard L Cohen <blc+@pitt.edu>
>To: Multiple recipients of list <radsafe@romulus.ehs.uiuc.edu>
>Subject: Re: FWD: A technique to measure DNA damage
>
>	--In the paper, they use it to study repair, which is of great
>interest for radiation health. They give a demonstration of adaptive
>response: the half life for repair of damage from a high radiation dose 
is
>cut in half by prior exposure to a low dose. This shows that low dose
>radiation stimulates repair processes. How does this square with the 
usual
>claim that any radiation is harmful? 
>
>


______________________________________________________
Get Your Private, Free Email at http://www.hotmail.com