[Dioxin-l] threshold dose?

[david bell]

Hi Jon
dioxin-induced degradation of the Ah receptor has been quite well know for 
some time, but very poorly understood. The reason the Roberts paper is novel 
and interesting (cited below), is that it shows how the dioxin receptor is 
destroyed rapidly. But many other papers have shown that the dioxin receptor 
is rapidly destroyed after activation by dioxin. I cite some below.

david

Degradation of the basic helix-loop-helix/Per-ARNT-Sim homology domain
dioxin receptor via the ubiquitin/proteasome pathway Roberts_BJ,
Whitelaw_ML JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, Vol.274, No.51, 
pp.36351-36356

Chen, H-S et al (1997) Archives Biochem Biophys 348: 190-198
Pollenz, R. S. (1996) Mol. Pharmacol. 49, 391–398
Prokipcak, R. D., and Okey, A. B. (1991) Can. J. Physiol. Pharmacol. 69, 
1204–1210
Reick, M. et al (1994) Mol. Cell. Biol. 14: 5653-5660



>David,
>
>      Do you have documentation on this? This is contrary to the published
>data on the receptor/dioxin binding that I have read up to this point.
>
>Jon
> > One of the things that has just become clear recently is that the
>activated
> > dioxin receptor (AhR) is destroyed (>90%) within one hour, even if 
>dioxin
>is
> > the activating agent. That is not to say the dioxin is destroyed, but 
>the
> > active receptor is- and so it stops signalling very rapidly.
> >
> > This starts to explain some of the differences between polycyclic
>aromatics
> > (PAHs), and dioxin- the AhR is switched on for just long enough to 
>destroy
> > the PAHs- at which point the AhR is all destroyed, and no more PAH is
> > available to switch on the AhR. By contrast, if there is a sufficient
>amount
> > of dioxin, it just keeps on activating newly synthesised AhR protein.

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