Caren C. Helbing talks with
ScienceWatch.com and answers a few questions about
this month's New Hot Paper in the field of Plant &
Animal Science. The author has also sent along images of
their work.
Article Title: The bactericidal agent triclosan
modulates thyroid hormone-associated gene expression and
disrupts postembryonic anuran development
Authors: Veldhoen, N;Skirrow, RC;Osachoff, H;Wigmore,
H;Clapson, DJ;Gunderson, MP;Van Aggelen,
G;Helbing,
CC
Journal: AQUAT TOXICOL
Volume: 80
Issue: 3
Page: 217-227
Year: DEC 1 2006
* Univ Victoria, Dept Biochem & Microbiol, POB 3055,Stn
CSC, Victoria, BC V8W 3P6, Canada.
(addresses have been truncated)
Why do you think the paper is highly
cited?
Triclosan is found in so many consumer products. Finding out that triclosan
can change how an important hormone works in the body at levels that we and
animals are exposed to is relevant to all of us.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
We focused on a native frog species and introduced sampling and analysis
methodologies that have broad applicability to other wildlife species.
Would you summarize the significance of your paper
in layman's terms?
Frogs act like "canaries in the coalmine" in water and wetlands. They are
very sensitive indicators of pollutants and tell us about the health of our
environment. They also tell us a lot about ourselves when it comes to
thyroid hormones. When a tadpole changes into a frog, thyroid hormones
trigger that amazing change.
In humans, many of the changes that occur in the frog tadpole are mirrored
in the developing fetus. Thyroid hormones are really important in proper
brain development for example. Thyroid hormones work in a similar way in
frogs, humans, and other vertebrates; so if triclosan is affecting how they
work in frogs, it is possible that other animals, including humans, could
be affected too.
How did you become involved in this research, and
were there any problems along the way?
I have a long-standing interest in how cells respond to their environment.
As a graduate student, I was introduced to the amazing changes that frogs
experience during their metamorphosis and I was hooked! I became fascinated
by how a single hormone, the thyroid hormone, can cause so many organs and
tissues to change in so many different ways—legs and lungs grow, the
tail and gills disappear, the brain and liver remodel—all in a
coordinated way, to turn a tadpole into a frog.
The fact that different tissues and organs respond to hormones in their own
ways also means that they could have different sensitivities to chemicals
that disrupt thyroid hormone action.
We still don't know how all this works, but a lot of it has to do with how
the genome (genetic code) is accessed and how proteins are affected. A big
challenge was to develop the right tools and methods to be able to sense
changes to proteins and to identify which genes may be important. We're
still working on improving this approach.
Where do you see your research leading in the
future?
A growing number of substances released into the environment have been
identified as disruptors of critical, normal hormone-dependent mechanisms
in humans and animals. These endocrine disruptors come from a variety of
sources such as plants, pharmaceuticals, pesticides, environmental
pollutants, and industry. The impact of these diverse compounds is
far-reaching; from effects on human and wildlife health to contributing to
wildlife population declines and resultant ecosystem imbalances.
Particularly vulnerable are those life stages where considerable modeling
or remodeling of existing body plans occurs such as in embryonic
development, metamorphosis, infancy, childhood and lactation. Thus,
exposure to endocrine disruptors at any of these critical stages could
result in permanent dysfunction, increased susceptibility to certain
cancers and reproductive problems reaching as far as multiple generations.
It is critical to have the appropriate tools in place to identify the
existence of endocrine disruptors in water samples (where most will
eventually end up) and to properly evaluate any endocrine disruptor risk in
chemicals that are to be released into our environment. Amphibians, fish,
marine mammals, bivalves, and other wildlife species are our sentinels.
"...help us
to understand why frog populations
are declining and guide us in
taking steps to protect our
environment."
By developing and using a wide range of molecular approaches that include
multi-species DNA arrays, quantitative real time PCR, and proteomic
techniques, we are uncovering the mechanisms of action of potential
endocrine disruptors and are gaining insight into how hormones function in
different tissues and species.
Critical to the normal development and maintenance of an organism's health
is ensuring that an appropriate balance is struck between two disparate
processes: cell proliferation and programmed cell death. Although a great
deal is understood about the machinery involved in both processes, the
factors that are critical in determining which pathway cells take is not
known, particularly when a single stimulus can simultaneously elicit both
outcomes.
A classic example of this is the normal postembryonic development of the
frog. A marked elevation of thyroid hormone (TH) levels triggers the rapid
and dramatic metamorphosis of the aquatic tadpole to a terrestrial juvenile
frog. The most obvious changes observed are the disappearance of the tail
and the growth of the legs. This program focuses on understanding how the
tail "knows" that it should die after receiving the triggering message from
TH.
We are particularly interested in the role that cell cycle regulating
proteins and phosphorylation may be involved in determining cellular
outcome. Since frogs are vertebrates, the knowledge obtained by studying
them can be easily applied to humans and, hence, will give us important
clues in the control of cell death and cancer.
There are many other chemicals and mixtures of chemicals that need to be
tested for possible effects on thyroid hormone action. We also need to get
a better idea on what part of the thyroid hormone signaling pathways are
most vulnerable to disruption. We need to develop new ways to define what
the pathways are in different tissues. In order to do this, we are
currently devising approaches based upon the power of transcriptomics,
proteomics, and metabolomics. These approaches will also help us to
understand why frog populations are declining and guide us in taking steps
to protect our environment.
Do you foresee any social or political implications
for your research?
The safety and quality of our environment and the products that we use are
of primary importance to people and wildlife alike. Our research is
important in helping to better assess risks posed within our complex
environment and also to work towards achieving sustainability and
stewardship of our waterways and water resources.
Caren Helbing, Ph.D.
Associate Professor and Michael Smith Foundation for Health Research
Scholar
Department of Biochemistry and Microbiology
University of Victoria
Victoria, BC, Canada
Keywords: triclosan, postembryonic anuran development, frog
populations, frog tadpole, thyroid hormones, hormone-dependent,
endocrine disruptors, water samples, plants, pharmaceuticals,
pesticides, environmental pollutants, industrial pollutants, wildlife
population declines, ecosystem imbalances, embryonic development,
metamorphosis, infancy, childhood and lactation, amphibians, fish,
marine mammals, bivalves, multi-species DNA arrays, quantitative real
time PCR, proteomic techniques, thyroid hormone (TH), transcriptomics,
proteomics, metabolomics, waterways, water resources