Linear No-Threshold Hypothesis

["GOLDIN, ERIC" <goldinem@songs.sce.com>]

     A couple of weeks ago, Mark Winslow from EPA requested opinions 
     and references regarding the linear no-threshold model (LNTM).  
     There were many responses related to the epidemiological studies 
     that attempt to demonstrate either an adverse effect from low 
     doses, no effect from low doses, or even a beneficial effect from 
     low doses.  There was very little reference to the possible 
     molecular evidence that shows that the model is at least 
     conservative, if not inappropriate, for occupational levels of 
     ionizing radiation exposure.
     
     This work below isn't mine, but, as one who formerly defined 
     myself as a radiobiologist (are we that rare in the HP ranks?), I 
     find molecular explanations valuable.  The data below are 
     excerpted from a Commentary Paper by Daniel Billen of Oak Ridge 
     Associated Universities in Radiation Research, 124 (242-245) 1990.
     
     Spontaneous DNA damage events/cell/hour        DNA damage/rad
     
               8,000                                   ~ 20
     
     
     Spontaneous DNA damage events/cell/sec        DNA damage/rad
     
                 2.2                                   ~ 20
     
     
     If failure to properly repair DNA damage is an initiating event 
     that leads to cell transformation (and eventually malignancy), 
     then the rate of damaging events is critical.  For occupational 
     dose rates which rarely exceed 1 rad/hr, the DNA damage rate is 
     overwhelmed by the rate of spontaneous damage (and repair).  For 
     acute radiation dose delivery (such as that experienced by the 
     survivors of Hiroshima and Nagasaki), the rate of 
     radiation-induced damage greatly exceeds the spontaneous rate and 
     probably the capability of repair.  For example, 100 rad (1 Gy) 
     delivered in a fraction of one second yields ~ 2,000 events 
     compared to only 2.2 events per second spontaneously.
     
     Therefore, while the data from acute dose survivors may be 
     linear, the data at chronic exposures are likely swamped by 
     spontaneous events (and the accompanying repair mechanism).  This 
     doesn't explain any cellular or tissue responses that account for 
     hormesis, but do indicate the basis for concluding that the risk 
     from occupational levels of radiation is "lost in the noise."  
     
     There are caveats in this argument: 
          Billen's table does not have data for spontaneous double     
          strand breaks.  
     
          One can't say that a particular event caused by              
          radiation cannot be the one damage that leads to             
          transformation.
     
          The rates of damage (and repair) are not consistent with     
          some known serious effects; that is, the tissue damage and   
          subsequent death of persons exposed to radioactive sources   
          (e.g. Mexico and Brazil) where the dose rates were not acute   
          (hence the DNA damage rates are likely less than the         
          spontaneous rate), yet over a period of many weeks to        
          months, severe cell death occurred.  Maybe cellular division   
          delay is a factor.
     
     One way to interpret these data is to assume, as Joyce Davis did, 
     that the dose response curve is a flattened J, with the bottom of 
     the J immersed in the background of spontaneous DNA damage.  There 
     are many reasons not to permit the uncontrolled spread of 
     radioactivity throughout our environment, and there are many 
     reasons to adopt reasonable occupational and public dose limits 
     (remember there are likely subsets of the population who are much 
     more radiosensitive than the average - for example those with the 
     gene for ataxia telangiectasia).  But we can certainly conclude 
     that the NRC public dose limits are conservative, and lower values 
     need not be applied to practices such as residual radioactivity 
     standards, air emissions, etc.
     
     Eric Goldin
     Southern California Edison
     goldinem@songs.sce.com
     Standard disclaimers apply