[Dioxin-l] threshold dose?

[Jon Campbell]

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
----- Original Message -----
From: "david bell" <burnt_paper@hotmail.com>
To: <dioxin-l@venice.essential.org>
Sent: Sunday, February 13, 2000 3:29 AM
Subject: Re: [Dioxin-l] threshold dose?


> > >4. Since dioxin is indestructible in the human body, and since dioxin
> > >molecules are extremely tenacious at the hormone receptor site (the
> >normal
> > >hormone destructor enzyme appears to have no effect) the gene continues
> >in
> > >an unusual ON or OFF state for the life of the cell.
>
> 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.
>
> cheers
> 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).
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