Archives: Spring 2000 Table of Contents
The 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 cancer.

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.

Brenda 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, WHOI

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 isn’t 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 other species.

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, or AhR.

"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 animal’s 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, "it’s not so good if you’re 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." It’s all about establishing the links, she says. "While I can’t help with the question ‘did this animal die of that?’ I can help to characterize the animal’s 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 animal’s toxic response to a contaminant.