Researchers find key to differences in dioxin sensitivity.

Oct 27, 2008

Head JA, ME Hahn and SW Kennedy. 2008. Key amino acids in the aryl hydrocarbon receptor predict dioxin sensitivity in avian species. Environmental Science and Technology 42 (19), 7535–7541.



Synopsis by Niladri Basu

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If other species of birds were as sensitive to dioxin-like compounds as chickens, then dioxins would kill them all. Dioxin-like compounds are toxic to most vertebrates, but significant differences in sensitivity exist among species. Scientists are beginning to understand the genetic variations that contribute to these differences.

 

Context

Dioxins, polychlorinated biphenyls (PCBs), furans and other dioxin-like compounds belong to a family of chemicals that are some of the most toxic on the planet. They cause cancer, birth defects, endocrine disruption and immune system problems. In the laboratory, parts per trillion levels (equivalent to 1 penny in 10 billion dollars) may cause these ill effects.

These chemicals are part of the ‘dirty dozen’– a group of 12 industrial chemicals now banned by most countries because of their extreme toxicity. Dioxins are by-products of human industries that use heat and chlorine, such as incineration and bleaching. PCBs were used in several industries as coolants and lubricants. Natural sources of dioxin-like compounds are forest fires and volcanoes.

Dioxin-like compounds are often referred to as ‘persistent organic pollutants’ or POPs, because of their unique chemical structures and biological properties. They do not break down easily in the environment and can persist for decades. They can travel long-distances via air or water. They are fat-loving molecules that tend to concentrate in animals and plants.

Inside cells, the dioxin compounds bind to a dioxin receptor (also known as the aryl hydrocarbon receptor or AHR). Binding sets off a series of cellular events that eventually lead to toxicity. Some species are more susceptible to their effects than others, which has puzzled researchers for decades.

Many environments are polluted by dioxin-like compounds. Some notable examples include the Tittabawassee River Basin and Saginaw Bay in Michigan (dioxins, furans) and the Hudson River in New York (PCBs). In these polluted areas, there is heightened concern that humans and wildlife are exposed to potentially harmful levels of these dangerous compounds. As such, many groups are trying to determine health risks of living in and near these polluted areas.

What did they do?

Lead-author Head and her colleagues wondered if sensitivity to dioxin-like compounds could be predicted by studying the dioxin receptor in birds. There is ample evidence that different species of birds can vary widely in their sensitivity to dioxin-like compounds.

First, the authors read and summarized the published scientific literature of research focusing on exposure to three compounds (dioxin, PCB 126 and PCB 77) in 12 different species of birds. They focused on toxicity studies where dioxin-like compounds were injected into bird eggs and choose studies with similar experimental designs. From this information, they determined if the species were or were not sensitive to health effects from dioxin-like compounds. Sensitivity was determined by comparing egg mortality among the species.

Next, the authors used genetic tools to assess the chemical composition of the dioxin receptor in each bird species. More specifically, they studied the region of the dioxin receptor responsible for binding the dioxin-like compounds. The authors compared the composition of the dioxin receptor with the published toxicity data.

What did they find?

In their literature survey, the authors found 12 bird species with a range of sensitivities to dioxin-like compounds. Ranked from most sensitive to least sensitive, the species were: chicken, ringed-necked pheasant, eastern bluebird, turkey, double-crested cormorant, American kestrel, common tern, wood duck, common eider, herring gull, Japanese quail and mallard. The sensitivity difference between chickens (most sensitive) and mallards (least sensitive) was greater than 1,000-fold.

The authors found that bird species that were the most influenced by dioxin-like compounds have a sensitive form of the dioxin receptor, and that bird species that were the least affected by exposure to dioxin-like compounds have an insensitive form of the dioxin receptor. The sensitive and insensitive forms of the dioxin receptor differed by two key building blocks (or amino acids) that affected the way that they interacted with dioxin-like compounds. Birds that were moderately sensitive to dioxin-like compounds had a third, intermediate, form of the dioxin receptor. The intermediate form of the receptor had one ‘sensitive’ building block and one ‘insensitive’ building block.


What does it mean?

Bird species have different variations of an important cell receptor that binds to harmful dioxin-like compounds. The receptors determine how vulnerable each species will be to health effects from exposure to the chemicals. The receptors, which have different chemical makeups, can be used as a tool to determine an animal's sensitivity to the harmful pollutants.

This work shows how basic science research can lead to results that can be applied to solve problems or used as a tool to monitor environments. The authors concluded that “this finding suggests that AHR genotyping might be useful as a genetic screen for predicting species sensitivity to dioxin-like compounds in contaminated ecosystems." The conclusion was based upon knowledge accrued from years of fundamental research aimed at understanding how dioxin-like compounds cause toxicity.

This work will lead to better ecological risk assessments. Most ecological risk assessments of dioxin-like compounds focus on toxicity data obtained from the chicken. However, as shown here, not all birds are created equally when it comes to dioxin-like compounds. The chicken is particularly sensitive. Basing risk assessments on the chicken could over-estimate the true health risks of exposure and lead to confusing results that jeopardize the validity of the entire risk assessment process.


Resources

Agency for Toxic Substances and Disease Registry. ToxFAQ for PCBs.

Karchner, SL, DG Franks, SW Kennedy and ME Hahn. 2006. The molecular basis for differential dioxin sensitivity in birds: Role of the aryl hydrocarbon receptor. Proceedings of the National Academy of Sciences 103:6252-6257.

Test for dioxin sensitivity in wildlife could result from new study. Science Daily May 18, 2006.

US Environmental Protection Agency. National Center for Environmental Assessment. Dioxins.

US Environmental Protection Agency. National Resources Damages. Ecological Risk Assessment.

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