Re: FW: Mice and elephants

[Vincent.King@DOEGJPO.COM (Vincent King)]

     So does a 1 Sv exposure lead to higher risks of radiation induced 
     cancers in sumo wrestlers than in jockeys or not???  (my version of 
     what I think was the original question - it's been a while)
     
     Seriously, one point is clear from the excellent and thought provoking 
     response below by Paul Unrau:  many of us are involved with practical 
     applications of radiation protection (meaning we no longer have close 
     ties with academia).  Our own education related to cancer causing 
     mechanisms (radiogenic or otherwise) is rudimentary at best and 
     sometimes decades old.  Unfortunately, occupational health physicists 
     and regulators do not have time to assimilate detailed information on 
     up to date developments in this area to help them "think like 
     biologists" more than they do.  How, then, can advances in radiation 
     biology be effectively translated into the process of promulgating 
     radiation protection regulations?  
     
     That bridge in knowledge must be improved upon if legitimate and 
     defensible alternatives to LNT are to be found for deriving dose 
     limits.  And until such alternatives are based on sound radiation 
     biology, it would be rash to scrap LNT -FOR STANDARD SETTING PURPOSES- 
     based on emotionalism alone (even if we do agree that it is not 
     representative of actual risk).  LNT may be a leaky boat, but what 
     does it do for our credibility if we abandon it for something no 
     better?
     
     Happy 4th of July (with apologies to our friends in the UK)!
     
     Vincent King
     vincent.king@doegjpo.com 


______________________________ Reply Separator _________________________________
Subject: FW: Mice and elephants
Author:  "Wood; Michael" <woodm@aecl.ca> at Internet
Date:    7/3/97 15:06


     
The following is the response to Bernie's "Mice and elephant" post from 
one of our senior Scientist.  As Paul is not on the list I am posting it 
for him.
     
Mike Wood
Radiation Biology and Health Physics Branch 
Chalk River Laboratories
Woodm@aecl.ca
     
     
>Practically no one expects one energy deposition event in one DNA molecule to 
>lead to cancer in either mice or elephants.  In fact, there is a reduction of 
>10^18 between the initial numbers of hits in DNA and the final probability of 
>a cancer even if all humans, for example, are held to be genetically 
>identical, which is absurd as the natural range of radiation resistance in 
>human populations is at least 7 fold.
>
>Mice in the wild have a half-life of about two weeks, so events which happen 
>in three years time are irrelevant - they are not under selective control. >So 
for a mouse, the possibility that a particular energy deposition event >leads 
to cancer, in nature, is irrelevant.  A difference in the probability >of 
repair of 10 or 100 fold (from 10^18 to 10^16) is irrelevant.  The number >of 
cell doublings separating a 30 gm mouse from a 2 tonne elephant is on the 
>order of 15-16.  For mice, there is less selective pressure to evolve high 
>fidelity control and repair systems, even though inbred strains in the lab in 
>fact show good controls, but for the elephant there is.  Getting to 
>10^11-10^12 cells successfully in the case of the mouse doesn't require the 
>same quality control that getting to 10^15-10^16 cells does in the case of 
>the elephant.
>
>For an elephant, the problem is simply to last the full 75 - 100 years in the 
>wild before dying.  Increasing the efficiency of DNA repair, or of 
>immunological cell surveillance by some amount makes this possible.  But even 
>for an elephant, the only selective advantage comes by pressure before and 
>during the age of reproduction.
>
>Small children are more sensitive because they are still growing, and clonal 
>events, which may arise at random or from energy deposition, have more cell 
>doublings in which to play out.  So a cell which loses a cancer repressor 
>gene has a better chance in a child of leading to a cancer.  Furthermore, the 
>only interesting thing about ionizing radiation as a carcinogen is that it is 
>entirely stochastic as to when DNA damage can occur in the cell cycle, and 
>some cells are always in a high risk part of the cell cycle.
>
>But in retinoblastoma, for example, cancers are present at birth, and do not 
>reflect ionizing radiation so much as simple chemical noise in systems which 
>use DNA for an informational molecule.  Shit happens.  
>
>So I have some questions for Bernie: 
>
>What sort of biology is it that doesn't take into account genetics, 
>development, and known aspects of the cancer risk process?  What sort of 
>biology is it that doesn't take into account the genetic uniqueness of each 
>sexually reproduced organism on earth?  What needs to be done to get 
>radiation physicists to think like biologists?  Is there any hope?
>
>Paul Unrau
>RB & HP Branch
>AECL
>UnrauP@aecl.ca
>
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