[Dioxin-l] threshold dose?

[Jon Campbell]

Dr. Bell,

     Could you tell us what happens to the dioxin once the complex of which
it was a part is destroyed? The paper that I cited yesterday seems to
indicate that dioxin is accumulated within the nucleus, as it is relatively
indestructible by normal human chemical processes. Assumedly it continues to
have some effect on the chemistry of the nucleus.

Thanks
Jon

PS I suggest you use your U of N address and show people your website. Very
impressive.
----- Original Message -----
From: "david bell" <burnt_paper@hotmail.com>
To: <dioxin-l@venice.essential.org>
Sent: Monday, February 14, 2000 6:54 PM
Subject: Re: [Dioxin-l] threshold dose?


> 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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