Angry Toxicologist

In one of the sessions today there was a fantastic talk by Dr Dolinoy. Here are my notes with some explainations where needed:

Epigenetics (this is where you affect gene expression by means other than damaging DNA, messing with transcription or translation of DNA/RNA, for instance).

If you give murine dams (mice mothers) genestein (a phytoestrogen that is part of soy) that would be equivalent to the higher end of what asians get, it effects the color of the coat after birth (a black female is crossed with a blond male). Basically this means that the genestein is affecting how the genes express themselves. In this case it is through methylation changes. Hmmm…what other genes are being changed.

Discussed BPA shortly. Noted that 95% of academic and gov’t studies find harm at low levels. 0% of industry studies do. Elicits chuckles from half the audience. The other half are scowly. He he he.

Did the same thing as genestein with Bisphenol A (BPA) at 50 mg/kg in food. Same result. Uh oh. Again, Hmmm…what other genes are being changed. The effects are from very early in gestation as the effects are found in all germ lines (types of cells that give rise to different organs).

Did same thing again but added BPA to methyl donors (folic acid and such). This has a control effect (brings the treated group back closer to controls). So, folic acid should keep some of the adverse methylation effects from occuring.

Coming up with list of genes that possibly could be affected by this mechanism: imprintome.

Seriously, can we stop using the suffix -ome? It’s so 2000 and it’s friggin’ annoying. I have added imprintome to my annoyome.

Planning on doing low doses to see if effects persist.

AT thinks: So if Folic Acid rescues BPA-induced methylation, does that mean that BPA could have the same effect as folic acid deficiencies? The implication here is that BPA exposure could, at some level, counter act folic acid and lead to things like Spinal Bifida, which is caused by folic acid deficits. Seriously, if anyone is fishing around for a disseration project for grad school, I just offered one up. That would be a pretty exciting avenue of research.

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Here are my notes on the next presetation, “The use of genetic variation to predict risk and efficacy during drug development”:

This guy is boring and slow.

I’m losing my will to live.

End of notes.

Comments

#1 Sandra Porter
March 17, 2008

Here’s the question that I would like answered: is it safe to use our Nalgene water bottles?

Do we really have to throw them away and switch to bottled water?
#2 Abel Pharmboy
March 17, 2008

Thanks, AT – I’ve followed Dana Dolinoy’s work for a few years and she completely kicks ass. Her mentor, Randy Jirtle, was most recently featured on NPR’s The People’s Pharmacy program. (Terra Sig link here).

Sandy, quite funny (not for Nalgene) that you mention the bottles we use while hiking. Nalge has taken some major sales hits with the BPA issue and, yes, it appears that one wants to stay away from #5 polycarbonate bottles.

Wish I was at SOT, AT – I’d buy you a plate of Dungeness crab!
#3 Cal Baier-Anderson
March 21, 2008

Hi Angry! I was also at the Dolinoy talk and want to add a bit of detail to your excellent post. The blonde mice were also obese, while the black mice were slim, so there is a metabolic pattern associated with the color, too. But more importantly, although genestein and BPA are both estrogenic chemicals, they had opposite effects – genestein increased the # of dark, slim mice, while BPA increased the number of blonde, fat mice! Folic acid given at the same time resulted in a more balanced mix of offspring.

But it really is a puzzle as to why two estrogenic compounds would have opposite effects. BPA still sucks, though.

The metabolic connection is really key – and the color is a marker for this connection.

And I believe I ran out of the room about a minute into the next talk – definite snoozer.
#4 shadow1515
March 25, 2008

is it safe to use our Nalgene water bottles?

I sure hope so. I use a Nalgene dispenser to hold my water for research. If anything is leaking into it, that could mean a whole year of work pretty much down the drain (or at least called into serious question).
#5 Blair
April 22, 2008

The Canadian Gov’t just made a major bisphenol A announcement
http://www.chemicalsubstanceschimiques.gc.ca/challenge-defi/bisphenol-a_e.html

The draft screening document is quite interesting of particular the info on page 70.

Any comments?
#6 muhabbet
March 26, 2009

thanks..
#7 hostgator
September 13, 2009

Thanks.
#8 Abercrombie
November 30, 2009

But it really is a puzzle as to why two estrogenic compounds would have opposite effects. BPA still sucks, though.

The metabolic connection is really key – and the color is a marker for this connection.

And I believe I ran out of the room about a minute into the next talk – definite snoozer.