AW: AW: [ RadSafe ] dose RATE of ANY Medicine is the decisive variable

[Muckerheide, Jim (CDA)]

Ted, Rainer, All,

Note that some LNT-advocates claim DSB differences from normal metabolism vs. radiation-initiated, esp. for direct effects with "more damage" and more likely electron affinity to a nucleotide (may be a specific one, guanine?) that damages the other strand in its transition.

Consider, however, that metabolic damage is not a homeostatic condition.  There are many stressors that have very high effects, from heat (including ingesting very hot liquids/foods), heavy exercise, high food intake, chemicals and medicines, tissue injury, etc. It's not clear to me how those "event" conditions with tissue damage and high-dose repair mechanisms (with "no pain, no gain") compare to low dose stresses.

But again, the DNA/cell damage isn't as important as the biological response mechanisms.  Also, as I noted before, the cell will not necessarily be "removed" whether apoptosis (absorbed) or necrosis (excreted as waste).  Instead, it may be inactivated and hang around but never divide to initiate a cancer.  It seems that measuring the number of translocations, etc., are poor indications of potential cancers.  They can be measures of dose (biodosimeter), but generally not a measure of health effects (an indirect measure at high doses only).  They are endpoints, not measures of damage with a potential for cancer initiation. (Although those confused about mechanisms vs. health effects for studies of cells in cultures, which are not immunologically whole, may claim that it is, just as they are confused about "bystander effects" as indicating an increase in health risk, though this seems to have been overcome in the last couple of years.)

Regards, Jim 


> -----Original Message-----
> From: Ted Rockwell [mailto:tedrock at starpower.net] 
> Sent: Friday, September 08, 2006 11:50 AM
> To: Rainer.Facius at dlr.de; Muckerheide-MA; Muckerheide-home; 
> Raabe, Otto; Long, Howard; radsafe at radlab.nl
> Cc: Rad-Sci-L; Rad_Sci_Health at yahoogroups.com; Pollycove, Myron
> Subject: Re: AW: AW: [ RadSafe ] dose RATE of ANY Medicine is 
> the decisive variable
> 
> 
> Thank you, Rainer.  That confirms my detailed discussion last 
> night with
> Myron Pollycove.  He notes that radiation does create more 
> double-strand
> breaks than metabolic and other chemical-type damage.  He has 
> conservatively
> assumed 2% double-breaks vs. one in ten thousand for 
> metabolic.  He tells me
> that the number for radiation has now been directly measured 
> and reported by
> two different researchers, each agreeing on a number like 
> 0.2%.  So it would
> take 100s of rad to produce as many double-breaks by radiation as are
> routinely produced by metabolism.
> 
> This says to me that the argument that "radiation is 
> different" has little
> real meaning.  And that is the fundamental point about my "realism
> argument"; radiation is not some mysterious, unknowable 
> phenomenon from
> which no "ordinary measures" can ever provide adequate 
> protection.  Nor does
> the "injured cell" lie around as a unique hazard to the body. 
>  It suffers
> the same fate as all other cells.  It dies and is replaced.
> 
> Otto: I am anxious to know whether you believe I am missing 
> something.  If I
> am right, your statement is a distinction without a difference.  No?
> 
> Ted Rockwell
> 
> 
> > From: <Rainer.Facius at dlr.de>
> > Date: Fri, 8 Sep 2006 16:53:58 +0200
> > To: <tedrock at starpower.net>, <Jim.Muckerheide at state.ma.us>,
> > <muckerheide at comcast.net>, <ograabe at ucdavis.edu>, 
> <hflong at pacbell.net>,
> > <radsafe at radlab.nl>
> > Cc: <rad-sci-l at wpi.edu>, <Rad_Sci_Health at yahoogroups.com>
> > Conversation: AW: [ RadSafe ] dose RATE of ANY Medicine is 
> the decisive
> > variable
> > Subject: AW: AW: [ RadSafe ] dose RATE of ANY Medicine is 
> the decisive
> > variable
> > 
> > Ted:
> > 
> > On the atomic/molecular level there may be a certain 
> fraction of primary
> > lesions (altered molecules) which do not arise in 'normal' 
> cell metabolism -
> > though of course I would refrain from claiming that we know 
> ALL about 'normal'
> > metabolisms. Experimentally we know that densely ionizing 
> radiation such as
> > heavy ions produces qualitatively - in contrast to 
> quantitatively - different
> > species of altered/damaged molecules (which by the way - 
> apart from other
> > reasons -invalidates the concept of RBE). To the extent 
> that some fraction of
> > deposited energy even from 'sparsely' ionizing radiation 
> leads to spatial and
> > temporal dense concentrations of ionizations it is not 
> unreasonable to claim
> > that also under low LET radiation molecular damage may 
> ensue which does
> > not/cannot arise in 'normal' metabolism.
> > 
> > Nevertheless, the prime message of virtually all findings 
> of the recent 'new
> > radiobiology' in my view is:
> > 
> > "Abandon hope all ye target theory modelers: on the effects 
> of low dose
> > exposures to ionizing radiation and other carcinogens" 
> [Jeffrey L. Schwartz,
> > Mutation Research 568(2004)3-4]
> > 
> > Viz, the initial molecular damage (even that to DNA) is in 
> NO WAY predictive
> > for the final biological result, (already) on the cellular 
> level, but
> > definitely on the tissue, organ, and whole system level. So 
> I would discard -
> > unless SPECIFIC molecular species and their SPECIFIC 
> pathways would be invoked
> > - this 
> > 
> > "Yeah, but radiation is different."
> > 
> > as the irrelevant hand-waving pseudo argument that is, 
> reflecting (with
> > hindsight) the state of knowledge 20+ years ago.
> > 
> > Kind regards, Rainer
> > 
> > 
> > ________________________________
> > 
> > Von: radsafe-bounces at radlab.nl im Auftrag von Ted Rockwell
> > Gesendet: Do 07.09.2006 21:43
> > An: Muckerheide-MA; Muckerheide-home; Facius, Rainer; 
> Raabe, Otto; Long,
> > Howard; radsafe at radlab.nl
> > Cc: Rad-Sci-L; Rad_Sci_Health at yahoogroups.com
> > Betreff: Re: AW: [ RadSafe ] dose RATE of ANY Medicine is 
> the decisive
> > variable
> > 
> > 
> > 
> > Jim:
> > 
> > I understand that much (I think), but is there a real 
> biological, and
> > logical, basis for saying that the processes involved in 
> radiation damage
> > (and healing, or progression to cancer)  are of a 
> fundamentally different
> > kind than damage from metabolism or other stimuli?  For if 
> they are, then
> > the whole Pollycove/Feinendegen argument fails.  I think a 
> lot hangs on the
> > validity, or invalidity of the argument (that seems to 
> trump all others)
> > that ³Yeah, but radiation is different.²
> > 
> > I¹d like to get really clear on that.
> > 
> > Ted Rockwell
> > 
> 
>