[Pharmwaste] Fish Glow Green After Genetic Engineering

Tue Apr 24 23:57:34 EDT 2012

Here below is some more information from a zebrafish study.  

The study below is not our work, but involves the work of Dr. MJ Barresi of
Smith College.  I received this from my colleague Dr. Theresa O'Keefe, Ph.D.

Theresa is currently performing some work with Dr. Barresi utilizing
zebrafish, but unfortunately this work has not yet been published.  Our
focus is on determining the toxicity of post-patient cytotoxins related to
out-patient Chemotherapy.  We are focusing on this because we believe there
are fewer than 25 of these cytotoxic materials which can have dramatic
impacts at trace level exposures, far below the therapeutic dose.  

As I am sure many readers know, it is not unusual for Chemotherapy patients
to receive several times these label dosages in a single infusion.  In the
US these out-patients return home to family and loved ones, usually with
absolutely no awareness of the post-patient risks arising from these
cytotoxic materials that they will excrete unaltered over 2 to 5 days.    

Our goal is to augment the German and Swiss studies and determine at what
trace levels these materials can have impacts on fast growing cells.  (We
know the official US exposure per NIOSH is zero, but we also can believe
there are millions of second-hand exposures each year.)  Our concerns are
our children, pregnant women and fetuses.  

Here is the study from Dr. Barresi: 

 <http://www.ncbi.nlm.nih.gov/pubmed/22462669> J Peripher Nerv Syst. 2012
Mar;17(1):76-89. doi: 10.1111/j.1529-8027.2012.00371.x.

Vincristine and bortezomib cause axon outgrowth and behavioral defects in
larval zebrafish.

 <http://www.ncbi.nlm.nih.gov/pubmed?term=%22Khan%20TM%22%5BAuthor%5D> Khan
TM,  <http://www.ncbi.nlm.nih.gov/pubmed?term=%22Benaich%20N%22%5BAuthor%5D>
Benaich N,
<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Malone%20CF%22%5BAuthor%5D>
Malone CF,
<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bernardos%20RL%22%5BAuthor%5D>
Bernardos RL,
<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Russell%20AR%22%5BAuthor%5D>
Russell AR,
<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Downes%20GB%22%5BAuthor%5D>
Downes GB,
<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Barresi%20MJ%22%5BAuthor%5D>
Barresi MJ,
<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hutson%20LD%22%5BAuthor%5D>
Hutson LD.

Source

Department of Biology, Williams College, Williamstown, MA, USA Department of
Biology, Smith College, Northampton, MA, USA Department of Biology,
University of Massachusetts, Amherst, MA, USA Program in Neuroscience,
Williams College, Williamstown, MA, USA.

Abstract

Peripheral neuropathy is a common side effect of a number of pharmaceutical
compounds, including several chemotherapy drugs. Among these are vincristine
sulfate, a mitotic inhibitor used to treat a variety of leukemias,
lymphomas, and other cancers, and bortezomib, a 26S proteasome inhibitor
used primarily to treat relapsed multiple myeloma and mantle cell lymphoma.
To gain insight into the mechanisms by which these compounds act, we tested
their effects in zebrafish. Vincristine or bortezomib given during late
embryonic development caused significant defects at both behavioral and
cellular levels. Intriguingly, the effects of the two drugs appear to be
distinct. Vincristine causes uncoordinated swimming behavior, which is
coupled with a reduction in the density of sensory innervation and overall
size of motor axon arbors. Bortezomib, in contrast, increases the duration
and amplitude of muscle contractions associated with escape swimming, which
is coupled with a preferential reduction in fine processes and branches of
sensory and motor axons. These results demonstrate that zebrafish is a
convenient in vivo assay system for screening potential pharmaceutical
compounds for neurotoxic side effects, and they provide an important step
toward understanding how vincristine and bortezomib cause peripheral
neuropathy.

C 2012 Peripheral Nerve Society.

PMID:

22462669

[PubMed - in process] 

I hope the links are supported on this ListServe.  

I have been a member of several ListServe for years and understand newcomers
can be disruptive.  I hope this post is not a violation of any conventions
or protocols.  

Thank you!  

Best Regards!  

John

-----Original Message-----
From: pharmwaste-bounces at lists.dep.state.fl.us
[mailto:pharmwaste-bounces at lists.dep.state.fl.us] On Behalf Of Tenace,
Laurie
Sent: Tuesday, April 24, 2012 10:18 AM
To: pharmwaste at lists.dep.state.fl.us
Subject: [Pharmwaste] Fish Glow Green After Genetic Engineering

<http://news.nationalgeographic.com/news/2012/04/120423-fish-glowing-polluti
on-bpa-environment-science/>
http://news.nationalgeographic.com/news/2012/04/120423-fish-glowing-pollutio
n-bpa-environment-science/

A genetically engineered fish that glows green from the inside out is
helping illuminate what pollutants do inside the body.

Endocrine disruptors are substances found in a wide range of industrial
products, including plastics, as well as in many female contraceptives.

The chemicals mimic the actions of sexual hormones, resulting in various
reproductive problems in both people and animals. Previous research has
shown the chemicals cause fish to change gender, and in people, endocrine
disruptors have been associated with lower sperm counts and breast and
testicular cancers.

Yet scientists have had difficulty tracking what endocrine disruptors do
inside a person or an animal's body. So a team genetically engineered
zebrafish to glow in places where an endocrine-disrupting chemical is
present-and thus show where it may be harming the body.

"We've essentially put genetic elements within the fish, over time, that are
specifically designed to identify where the chemicals penetrate and act
within the body," said study leader Charles Tyler at the U.K.'s University
of Exeter.

"This genetic machinery produces proteins which don't interfere with the way
these chemicals act in the body, but they fluoresce green under a
fluorescent microscope, providing a reporting system to identify which body
tissues are being affected.

"This, in turn provides a more 'intelligent' way of identifying where the
[pollutants'] potential health impacts might be" in people.

(See "Glowing Animals: Beasts Shining for Science.")

Glowing Fish Confirm Past Findings

Tyler and team exposed the zebrafish to varying levels of chemicals known to
affect the hormone estrogen, including ethinyloestradiol, found in
contraceptive pills; nonylphenol, present in paints and industrial
detergents; and bisphenol A (BPA), a component of many plastics.

All of these substances have become common freshwater pollutants that are
connected to problems such as gender changes in fish and decreased fertility
and increased cases of cancer in people. (Related: "Sex-Changing Chemicals
Found in Potomac River.")

The researchers exposed the fish to different endrocrine disruptors at
varying concentrations, and then used a microscope to see which of the small
fish's organs glowed-and thus responded-to the chemicals.

The data should help identify the thresholds at which the chemicals affect
various tissues and organs in the body.

For instance, observing the glowing fish confirmed previous findings, such
as a link between bisphenol A and heart problems.

"We do see in this fish that the heart glows particularly in response to
bisphenol A," Tyler said. "So we can target the heart and try to look at the
mechanics of what is happening."

(Related: "Chemical BPA Linked to Heart Disease, Study Confirms.")

Tyler and colleagues also watched the chemicals light up other parts of the
fish's anatomy, including its eyes and skeletal muscles.

"It's often been assumed that these chemicals impact the liver or testes or
ovaries, but in these fish we've identified them in many different tissues,
including parts of the brain," he said.

For now, the fluorescent technology is limited to fish younger than six days
old, because their skin has yet to develop pigmentation that would interfere
with observing the fluorescence.

"The next phase is breeding these fish with a strain that lacks pigment in
the skin," which would allow the team to observe the fluorescent reactions
in adult fish as well, Tyler said.

Laurie Tenace

Environmental Specialist III

Waste Reduction Section

Florida Department of Environmental Protection

2600 Blair Stone Rd., MS 4555

Tallahassee FL 32399-2400

P: 850.245.8759

F: 850.245.8811

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