Spring 2000 Table
Link Between Environmental Contaminants and Animal Susceptibility
by Tracey I. Crago, WHOI Sea Grant
Imagine you are walking by a well-known
research laboratory. The sign in the window reads: Wanted: volunteers
for a scientific experiment. Inquire within.
A strong supporter of science, you
realize that this could be a chance to contribute something important
to the field. You decide to find out more and listen while a doctoral
student goes over the details:
You would be one of three species of
mammals to be tested for susceptibility to an environmental contaminant.
The other species will be a beluga whale and a mouse. The contaminant
to which you will be exposed is TCDD, which stands for 2,3,7,8-tetrachloro-dibenzo-p-dioxin.
The research is very important because, heretofore, scientists have
not been able to separate the possible effects of such contaminants
from those of other factors, like viruses or natural toxins.
Just as you take out your pen to sign
your waiver, the student mentions that TCDD is the most potent representative
of a class of environmental contaminants known collectively as planar
halogenated aromatic hydrocarbons, or PHAH. After exposure to these
contaminents, vertebrate animals-including mammals, birds,
and fish-have displayed a host of problems, ranging from skin
lesions, developmental abnormalities, endocrine disruption, and
Before the student can finish, you
realize that this may not be the opportunity you were hoping for.
In real life, scientists who study
risks-such as those associated with susceptibility and exposure
to environmental contaminants-face many challenges. The scenario
described above could not take place for a number of reasons, including
legal and ethical concerns prohibiting the direct testing of toxic
chemicals on humans and protected animals such as marine mammals.
Yet the challenge of understanding if and how chemical contaminants
affect various species is critical to the development of effective
risk assessment and protective measures that will eliminate, reduce,
or regulate the exposure to environmental contaminants.
Jensen is finishing her Ph.D thesis, investigating the susceptibility
of marine mammals, particularly beluga whales from the St.Lawrence
estuary, to environmental contaminants. Photo: Eli Hestermann,
Mark Hahn is a WHOI toxicologist who
studies the effects of environmental contaminants on fish, mammals,
and birds. For the last decade, Hahn has received Sea Grant support
to employ molecular and cellular techniques to detect the presence,
susceptibility, and effects of contaminant exposure. In a recent
study, Hahn enlisted MIT/WHOI joint program student Brenda Jensen
to investigate the potential for PHAH to cause toxic effects in
belugas. To do this, they are examining key biochemical players
in the toxic response.
Belugas and other species or populations
of marine mammals are known to accumulate contaminants, including
PHAH, in their fat stores and other tissues. It has been suggested
that exposure to PHAH and other organic contaminants by vertebrates
may result in immunosuppression, reproductive toxicity, and cancers.
Beluga whales from the St. Lawrence Estuary, for example, are among
the most heavily contaminated population of marine mammals. The
presence of chemicals in St. Lawrence belugas-the same chemicals
known to exist in the St. Lawrence region-has been blamed for
failure of the population to recover from hunting-related declines
at the beginning of the 20th century.
And, while that may seem clear-cut,
it isnt a foregone conclusion, say Hahn and Jensen. Until
scientists can provide a mechanism and show a cause and effect relationship,
says Jensen, the presence of chemicals is merely coincident with
the observed health problems. For example, the actual cause of death
might be disease, and slow rate of reproduction might be the actual
reason for slow population recovery. "Many feel that chemicals may
contribute to these processes," says Jensen, "but the trick is to
establish that link."
Because direct testing of marine mammals
and humans is illegal, scientists must take alternate approaches,
including extrapolation from studies of contaminant exposure in
Extrapolation plays a key role in the
research of Hahn and Jensen. That process, says Hahn, is most accurate
when scientists combine fundamental knowledge of biochemical and
molecular processes with specific information on the way those processes
are regulated within a particular species. "In order to predict
the nature and severity of effects that might result from exposure
of marine mammals to environmental contaminants," says Hahn, "it
is important to understand the characteristics of biochemical systems
that determine susceptibility to these chemicals."
That is precisely what Hahn and Jensen
are doing. By looking at a highly sensitive protein known to be
present in most, if not all, vertebrate species, they are seeking
to understand the complex cellular-level processes that occur within
belugas. The protein is known as the aryl hydrocarbon receptor,
"The AhR," says Jensen, "may represent
a way to figure out the overall sensitivity [of a species] to toxic
compounds. It is the presence of the AhR that makes TCDD, and possibly
other compounds, toxic to a species." (A 1996 study using mice,
in which the AhR was removed, rendered the mice insensitive to TCDD
exposure.) As such, it serves as a good biomarker, or indicator,
of contaminant susceptibility.
To test an animals sensitivity
to TCDD, Hahn and Jensen are closely examining the characteristics
of its AhR. They perform an assay, or test, to measure binding affinity.
Essentially, they look to see if the AhR protein binds to a ligand,
or molecule, of the TCDD and, if so, how tightly they bind. The
tighter the bind, the higher its binding affinity, which can be
interpreted as higher sensitivity to TCDD.
In the laboratory, Hahn and Jensen
have measured binding affinity of the beluga AhR. To conduct the
assay, Jensen compared the affinity of the beluga AhR to that of
dioxin-sensitive mouse AhR and lower-affinity human AhR. The results,
not yet published, clearly show that the beluga affinity was "at
least as high as the high-affinity mouse AhR and substantially greater
than that of the human AhR.
"While that may be good for me," says
Jensen of her findings, "its not so good if youre a
beluga." The findings are consistent with the high incidence of
disease in St. Lawrence belugas, and suggest that belugas, as a
species, are highly sensitive to contaminant exposure.
"The levels of PHAH contaminants in
the marine environment are rarely high enough to kill an animal
outright," says Jensen. "These contaminants exert their effects
by interrupting other processes and, sometimes, cause them to fail."
Its all about establishing the links, she says. "While I cant
help with the question did this animal die of that?
I can help to characterize the animals AhR. And that," she
says, "may be a key for understanding the susceptibility of a species
to PHAH, which, in turn, may help us better understand the health
ramifications of the contaminant burdens that we see in animals
and in the environment."
Rest assured, neither Hahn nor Jensen
will be looking for volunteer subjects to help them achieve their
goal of better understanding the complex biochemical processes that
govern an animals toxic response
to a contaminant.