Re: DOSE RATES AND RAD. EFFECTS

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

> 	I agree with John that immunosuppression will be different 
> (lower) for 500 rads delivered at 8 rads per minute when compared 
> to 500 rads delivered at 70 rads per minute.  In fact, the "effect" may 
> go to zero as the dose rates get smaller and smaller.  Some in 
> our community even believe that the immune system is "stimulated" by 
> low dose rate radiation.

This issue has actually been studied fairly intensively as part of the 
preclincial studies for bone marrow transplantation.  In fact, the dose 
required for immune suppression does not decrease very fast as the dose rate 
is lowered.  You can certainly get good immune suppression in mice for dose 
rates as low as 0.5 rad/min (see for example, Fu et al, Radiol 114:709, 1975).

Of course, while 0.5 rad/min is a very low dose rate by therapy standards, it 
is a rather high dose-rate by protection standards.

> Dose rate effects are well known for most (all?) biological end points.  

True for low LET radiation, endpoints that depend on cell killing, and dose 
rates in the 0.5 to 500 rad/minute range; but I would not _assume_ that this 
means that the same is true for non-cytotoxic endpoints, high LET radiation 
and/or lower dose rates.

> There seems to be universal acceptance 
> among informed scientists that the effects also exist for 
> radiation induced cancer in humans.

Yes, but...
- the magnitude and shape of the dose-rate relationship is not known
- there is essentially no data (perhaps none at all) at the dose rates that 
are really of interest for radiation protection

> Dose rate effects are something we all should think about 
> as we contribute to the knowledge pool regarding the effects of 
> radiation on humans.

Agreed, but I don't think that the "high dose" dose rate studies done in 
radiotherapy-oriented radiobiology are of much relevance to the debate.

In fact, I'm not sure that laboratory radiobiology is much of any real use in 
the LNT debate, because most of the argument is about the shape of the dose 
response curve at dose and dose rates at which no effects can be demonstrated 
in the laboratory.  Remember, that in the laboratory is is extremely difficult 
to demonstrate any low-LET radiation effects below a total dose of about 10 
rad.

Maybe those who would debate the LNT vs no-LNT need to be reminded 
periodically that they are arguing about the shape of the dose-response curves 
for doses below which it is possible to directly detect statistically 
significant biological effects.



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