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Small fish offer big potential to treat parasitic disease

Zebrafish
And other discoveries that keep us healthy

The parasite Toxoplasma gondii is the reason pregnant women are told to avoid cats’ litter boxes. The microbe, excreted by cats in their feces, can transmit the disease toxoplasmosis to the fetus, sometimes resulting in severe brain damage or death. Toxoplasma gondii is one of the most common parasites in the world, estimated to infect about one-third of people on earth. Toxoplasmosis is readily treatable, however the parasite remains dormant in the body for the person’s lifetime, often in the brain, spinal cord, and eye. There are currently no drugs available to treat this chronic stage of the parasite and the potential for reoccurrence of acute infection due to immune suppression. There is also growing evidence that the chronic stage of T. gondii may play a role in numerous neurological and psychological disorders.

Oregon State University microbiologists have shown that zebrafish can be infected with Toxoplasma gondii, a discovery that could lead to new drugs for this common, sometimes deadly, infection. Zebrafish are an excellent model for biomedical research because they are transparent during development, mature rapidly, and share about 80 percent of their genes with humans. This allows scientists to test hundreds of compounds in a short period of time.

View the Sinnhuber Lab 360

View OSU's Sinnhuber Aquatic Research Lab in 360 degrees. (360 by Stephen Ward.)

OSU’s Sinnhuber Aquatic Research Laboratory is one of the world’s foremost facilities for biomedical research using zebrafish research models.

“This advance may provide a very efficient tool for the discovery of new therapies for T. gondii,” said Justin Sanders, an OSU researcher and lead scientist on the study. “With it we should be able to screen a large library of compounds, at much less expense, and examine things that have never been considered as possible treatments for this parasitic disease.”

A faster, better assessment of cancer risk

Scientists at OSU’s College of Agricultural Sciences have developed a faster, more accurate method to assess cancer risk from common environmental pollutants. Their research focuses on a class of pollutants known as polycyclic aromatic hydrocarbons, or PAHs, that occur as chemical mixtures when organic material is burned.

“Rather than waiting 25 weeks for tumors to develop, we could predict after only 12 hours the ability of certain PAH mixtures to cause cancer,” said Susan Tilton, an OSU environmental toxicologist. The new method is not only quicker, it also produces more accurate cancer-risk assessments than are currently possible.

Researchers found that they could analyze the immediate genetic responses of skin cells of exposed mice and apply statistical approaches to determine whether or not those cells would eventually become cancerous. This will be particularly useful for screening hundreds of different kinds of PAHs, some of which are known carcinogens, but many of which have not been tested.

Tilton’s team examined three PAH mixtures that are common in the environment—coal tar, diesel exhaust, and cigarette smoke—and various mixtures of them. They found that each substance touched off a cascade of biological changes in the skin cells that amounted to a unique “fingerprint” as cells reacted to each chemical. By matching these patterns with known changes in cancerous cells, they found they could identify developing cancers much earlier and more accurately.

“Our study is a first step in developing more accurate methods to test mixtures as a whole instead of individual chemical components,” Tilton said. The study was supported by the National Institute of Environmental Health Science’s Superfund Research Program in collaboration with the Pacific Northwest National Laboratory.

Toxins beneath your feet

Pavement sealcoats are meant to make driveways, parking lots, and playgrounds last longer and look better. However, new research from OSU’s College of Agricultural Sciences indicates that coal-tar based sealcoats are significantly more toxic and mutagenic than previously suspected.

The culprits are polycyclic aromatic hydrocarbons (PAHs). Coal-tar pitch, a known human carcinogen, contains about 200 different PAHs. These chemicals can find their way into soils, storm drains, and even house dust, as the sealcoats are abraded by car tires and volatilize into the air. A study by the US Geological Survey in 2011 reported that house dust in homes adjacent to pavement with coal-tar based sealcoat had PAH concentrations 25 times higher than those normally found in house dust.

This earlier research has been controversial, with some industry groups arguing that the federal study overstated the risks. The new OSU study indicates that previous research has, if anything, understated the risks. The OSU program studying PAHs, supported by the National Institute of Environmental Health Science’s Superfund Research Program, is one of the most advanced of its type in the world, and can identify and analyze more than 150 types of PAH compounds. The OSU researchers examined the presence and biologic activity of a much greater number of PAHs in sealcoats than has been done in any previous research. Their examination of those PAHs, done with a zebrafish model that closely resembles human reaction to toxic chemicals, showed developmental toxicity to embryos.

In addition, the study showed that sealcoats based on asphalt, more commonly used in the West, were still toxic, but far less than those based on coal tar that are more commonly used in the Midwest and East.

“This should assist individuals and municipalities to make more informed decisions about the use of sealcoats and weigh their potential health risks against the benefits of these products,” said Staci Simonich, an OSU environmental chemist. “And if a decision is made to use sealcoats, we concluded that the products based on asphalt are significantly less toxic than those based on coal tar.”

Published in: Innovations, Health