Re: Radiation - net benefit or detriment?

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

 > All the quantitative work I have seen with radiation induced DNA
 > double-strand breaks (DSBs) point at a linear induction with increasing 
radiation dose
---
However, it is estimated that chemical and thermal effects induce about 200 
DSBs per cell per year, whereas 10 rem of radiation per year induces only 
about 4 per cell per year, so the contribution of low level radiation to the 
body's DSB accumulation is relatively negligible. This suggests that we 
consider the positive effects of low level radiation - stimulation of immune 
system, stimulated production of repair enzymes, etc - as relevant factors 
in deciding whether the net effect is good or bad.
------------------------------------------------
For red bone marrow a normal frequency of misrepair events per stem cell and 
year has been estimated to about 0.5. Most of this is probably not due to 
ionizing radiation damage. 1-2 DSBs/stem cell and year is assumed to be the 
result of normal background radiation. Some of these can be expected to 
contribute to the mutation frequency.

It is central however to notice that many of the DSBs arising from normal 
metabolsim of the cell etc probably are the result of two SSBs (or an SSB 
next to base damage that is processed through an SSB step) on opposite DNA 
strands. Most of these DSBs are probably quite trivial for the cell to 
repair (as well as those which result from topoisomerase activity).

This contrasts the complex DSBs of the kind that have been named LMDS (after 
prof. John Ward in San Diego). LMDS probably in turn fall into different 
subcategories where some of them may represent large deletions (lost loops 
etc). Depending on cell cycle stage and perhaps other factors these DSBs can 
be processed by principally different mechanisms. Those based on a 
recombination process with the backup (homologuous) chromosome may produce 
complete restoration whereas the DNA-PK system (end-joining) seems to result 
in loss of DNA information. The latter seems to be an important repair 
pathway (taking care of more than 50 % of the DSBs in human cells?).

SSBs are produced by a rate of about 100 000 per cell and day in mammalian 
cells. An LD50 SSB level for mammalian cells seem to be in the order of 2 
million simultaneously occurring SSBs (there may be an important variation 
between different cell types/tissues and a dependence of other factors). 
This LD50 may very well be related to a rare occurrence of closely occurring 
SSBs in opposite strands.

The relative fractions of various classes of DSBs repaired by recombination 
or other pathways has not yet been clarified. Before that has been done one 
should be cautious about the interpretations. There is probably a long way 
(at least a few decades) from this level to consistency with epidemiological 
data. Remember the bystander effects, the survival curves found by P. 
Lambin, M. Joiner and others, genomic instability among other newer 
findings.

Please add or correct any relevant information that you may have.

My personal reflections only,

Bjorn Cedervall    bcradsafers@hotmail.com

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