Dioxin or "aryl hydrocarbon" source

Bernard Murray bernard at elsie.nci.nih.gov
Wed May 8 02:33:33 EST 1996

In article <djt2-0705961410520001 at path22285.path.cwru.edu>, djt2 at po.cwru.edu 
>For our studies of the aryl hydrocarbon (AH) receptor we need to obtain
>some ligand.  Most folks in the literature use "dioxin" or similar.  I
>haven't been able to find either "dioxin" or any of the chemical names
>used in the typical supply catalogs, e.g. Sigma, Calbiochem, etc.  I have
>a feeling that I'm looking too hard and missing an obvious source (maybe
>"coal tar"?)
>I'd appreciate a pointer to a source for this chemical.

Dioxin (TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin) is evil stuff
due to its toxicity and also because it is just so hard to get rid
of (I think you have to use high intensity UV light).  It is thus
pretty hard to get hold of and you should check your local safety
people before you do so.  The best source is to beg it from people
who work with it as I do not think it is available commercially but
it may still be availble from the NCI Chemical Carcinogen
	Other halogenated biphenyls (especially the brominated versions)
are a little easier to come by and some of them approach the
sub-nanomolar Kd of TCDD for the Ah receptor.  Again, the NCI
would probably be a good starting point but I believe there may be
specialist chemical companies selling them (cue the posting from
the BioSupplyNet people...).
	Anyway, if you can make do with compounds with lower Kd
values then you could shift to polycyclic aromatic hydrocarbons.
The usual choice is 3-methylcholanthrene (which some companies
call 20-methylcholanthrene) whilst some people plump for
benzpyrene or benzanthracene.  I used to use 3MC from Sigma.
	If toxicity is your worry then you'll probably have to use
beta-naphthoflavone (5,6-benzoflavone) which is considerably less
potent than TCDD and also is less specific as you will see
induction of non-Ah battery genes such as GST-Ya.  If you are using
this in vivo you have to pay much more attention to the kinetics.
I've used BNF from Aldrich.
	I will not point to any particular references on the
subject as the field is around 30 years old and the literature
is immense.  I also feel that if I mentioned a few names I
would be leaving out too many that are equally important.

	One worry is that the changes in protein kinase activity
elicited by dioxin treatment may not be related to the Ah receptor
(certainly some changes can be induced in enucleated cells) so
maybe you have to go with dioxin itself and other ligands may not
work for your purposes (I guess only you know what question you are
trying to answer) but basically there are many halogenated biphenyls
that are characterised as active or inactive at the Ah receptor and
there's plenty of SAR data out there.

(No, I'm not surprised a protein kinase group is working on the
Ah receptor as some Ah groups have made the reverse excursion)

	Good luck with your search..

Bernard Murray, Ph.D.
bernard at elsie.nci.nih.gov  (National Cancer Institute, NIH, Bethesda MD, USA)

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