Re: Mice Irradiation Questions

["John Moulder" <jmoulder@post.its.mcw.edu>]

> A researcher here at Montana State University has proposed to irradiate 
> a few dozen mice to 500 rads each.  The purpose of this exercise is 
> to enhance post-irradiation implanted tumor growth... 
>  
> Most of the literature that we are looking at does not describe the 
> dose rate used in preparing mice for tumor implantation.  Nearly 
> all indicate a dose of 500 rads, although one article suggests a dose 
> of 150 rads given at a dose rate 70 rads/min. 

The dose rate matters very little as long as it is above about 50 rad/minute, 
and is delivered continuously.

> How critical is the "acuteness" of the dose given to the mice (in order 
> to achieve the desired effect).  Given target uniformity 
> considerations, the highest dose rate I can produce with our 
> "irradiator" (naval radiac calibrator AN/UDM-1A) is a little over 8 
> rads/minute. 

This dose rate is low enough that you will see a dose rate effect.  That is, 
the 500 rad will not be as "effective" as the above cited paper that used 70 
rad/min.

> Obviously, before we proceed we want to be reasonably confident that 
> we'll obtain positive results.  For those who have experience in this 
> area, will our system work (or will the dose rate limitation 
> compromise this undertaking)? 

It should work, but you may have to adjust the total dose to get the desired 
effect.  The solution is for the investigator to define what the endpoint is, 
then do a dose-response curve at the highest dose rate you can get.

If you are trying to reproduce what someone else has done, then you have a 
problem because 8 rad/min is just not biologically equivalent to 70 rad/min.


> One more question: 
>  
> There are mice available that have been bred to express 
> immunodepression (apparently there are some transgenic lines available 
> as well).  However, despite the phenotype, these mice do not sustain 
> and promote implanted tumor growth as well as mice that have 
> received significant doses of radiation. 
> Not having explored this realm of radiation biology much, what 
> "other radiation induced factors" are at play here? 

This depends a lot on the type of tumor and its relationship to the host.  
When a tumor arises in an inbred strain of animals, it can generally be freely 
transplanted to any other animal in that strain, and pre-irradiation of the 
host will make little difference (this is a nonimmunogenic tumor model).  
However, then a tumor is transplanted to another strain, there will usually 
(always?) be an immune response, and pre-irradiation will enhance tumor growth 
(this would be an immunogenic tumor model).

Note that the best current data is that human tumors are non-immunogenic, and 
hence that immunogenic animal tumor models have little relevance to human 
tumor therapy.

If the mice are sufficiently genetically immune incompetent, then you can grow 
just about any tumor in them, even a human tumor.  Athymic nude mice, are 
immunocompromised, they will allow many tumors to grow, but irradiating the 
host helps.  SCID mice, however, will grow just about any type of tumor, and I 
don't think preirradiation makes much difference.


John Moulder (jmoulder@its.mcw.edu)
Radiation Biology Group
Medical College of Wisconsin