This is an Oregon State University press release from 5-8-15 that shares about the collaborative research project of Project 1 and Core C – Biostatistics and Modeling.

– By Gail Wells, 541-737-1386, gail.wells@oregonstate.edu, on Twitter @OregonStateExt
Source: Susan Tilton, 541-737-1740, susan.tilton@oregonstate.edu
http://bit.ly/OSU_AgNews1542

CORVALLIS, Ore. – Scientists at Oregon State University have developed a faster, more accurate method to assess cancer risk from certain common environmental pollutants.

Researchers found that they could analyze the immediate genetic responses of the skin cells of exposed mice and apply statistical approaches to determine whether or not those cells would eventually become cancerous.

The study focused on an important class of pollutants known as polycyclic aromatic hydrocarbons, or PAHs, that commonly occur in the environment as mixtures such as diesel exhaust and cigarette smoke.

Dr. Susan Tilton
Dr. Susan Tilton

“After only 12 hours, we could predict the ability of certain PAH mixtures to cause cancer, rather than waiting 25 weeks for tumors to develop,” said Susan Tilton, an environmental toxicologist with OSU’s College of Agricultural Sciences.

For at least some PAH mixtures, the new method is not only quicker but produces more accurate cancer-risk assessments than are currently possible, she said.

“Our work was intended as a proof of concept,” said Tilton, who is also affiliated with the OSU’s multidisciplinary Superfund Research Program, a center funded by the National Institute of Environmental Health Sciences (NIEHS).

“The method needs to be tested with a larger group of chemicals and mixtures. But we now have a model that we can use to develop larger-scale screening tests with human cells in a laboratory dish.”

Such a method will be particularly useful for screening PAHs, a large class of pollutants that result from combustion of organic matter and fossil fuels. PAHs are widespread contaminants of air, water and soil. There are hundreds of different kinds, and some are known carcinogens, but many have not been tested.

Humans are primarily exposed to PAHs in the environment as mixtures, which makes it harder to assess their cancer risk. The standard calculation, Tilton said, is to identify the risk of each element in the mix – if it’s known – and add them together.

But this method doesn’t work with most PAH mixes. It assumes the risk for each component is known, as well as which components are in a given mix. Often that information is not available.

This study 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 rapid and distinctive cascade of biological and metabolic changes in the skin cells of a mouse. The response amounted to a unique “fingerprint” of the genetic changes that occur as cells reacted to exposure to each chemical.

By matching patterns of genetic changes known to occur as cells become cancerous, they found that some of the cellular responses were early indicators of developing cancers. They also found that the standard method to calculate carcinogenic material underestimated the cancer risk of some mixtures and overestimated the combined risk of others.

“Our study is a first step in moving away from risk assessments based on individual components of these PAH mixtures and developing more accurate methods that look at the mixture as a whole,” Tilton said. “We’re hoping to bring the methodology to the point where we no longer need to use tumors as our endpoint.”

Tilton collaborated on the research with Katrina Waters of the Pacific Northwest National Laboratory, and others. Their findings appeared in a recent edition of Toxicological Sciences.

The study was funded by NIEHS, which supports the Superfund Research Program, a multi-partner collaboration that includes OSU and PNNL.

Congratulations to the lab of Dr. Robert Tanguay, Project 3 Leader!
The manuscript, Multidimensional In Vivo Hazard Assessment Using Zebrafish, accepted October 2013 in Toxicological Sciences, has been published in the January 2014 journal (in the Safety Evaluation section) with an Editor’s Highlight.

January 2014 Toxicological Sciences journal
January 2014 Toxicological Sciences journal

The Tanguay group uses the embryonic zebrafish model to demonstrate the utility of high throughput screening for toxicology studies. The group evaluated the 1060 US EPA ToxCast Phase 1 and 2 compounds on 18 distinct outcomes. With four doses for each compound the group generated a dizzying number of data points highlighting the importance of bioinformatics analysis in these types of studies. The study shows how it is now possible to screen many of the tens of thousands of untested chemicals using a whole animal model in which one can literally see developmental malformations. —Gary W. Miller

Abstract

There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2 compounds using the embryonic zebrafish and found that 487 induced significant adverse biological responses. The utilization of 18 simultaneously measured endpoints means that the entire system serves as a robust biological sensor for chemical hazard. The experimental design enabled us to describe global patterns of variation across tested compounds, evaluate the concordance of the available in vitro and in vivo phase 1 data with this study, highlight specific mechanisms/value-added/novel biology related to notochord development, and demonstrate that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies.

rb_210_img3Learn more about Tanguay’s zebrafish research

 

By Steven O’Connell (Student, Project 4)

SOConnell_SRPPost
Steven O’Connell sampling at the Portland Harbor Superfund Site

In the past few years, our Center has been conducting research to learn more about oxygenated polycyclic aromatic hydrocarbons (OPAHs). OPAHs are one of the degradation products of parent PAHs. OPAHs are studied because they are present in the environment and pose an unknown hazard to human health.

Although OPAHs have been measured in several samples all over the world, most analyses contained only a handful of OPAHs or used methods that may be inaccurate.  To address some of the analytical challenges measuring OPAHs, I was involved in a multi-year study: An Analytical Investigation of 24 Oxygenated-PAHs (OPAHs) using Liquid and Gas Chromatography-Mass Spectrometry.

Why is there a focus now on OPAHs?

Focus on this class of compounds has really increased in the last few years, although it’s interesting to note that there were reports of some of these compounds in the 1970’s and earlier.  There are several reasons researchers want to study these compounds.  OPAHs seem to be found in similar concentrations to the highly studied parent PAHs in a variety of samples ranging from diesel exhaust to urban air.  Additionally, not a lot is known about the toxicity of these compounds, although early evidence suggests that they may be on par with PAHs.  That’s why the OPAH research of students Andrea Knecht and Britton Goodale in Dr. Robert Tanguay’s Lab (Project 3) has been so important.

Why measure OPAHs at the Portland Harbor Superfund Site?

It makes a lot of sense to try and measure OPAHs at Portland Harbor Superfund. PAHs have been responsible for remediation at some sites for years now, and are the precursors of OPAHs.  In some cases, remediation approaches employ ultra violet (UV) light to try and degrade PAHs and thereby cleanup that site.  However, it is possible that PAHs could degrade to OPAHs during the process.  If no one is monitoring the products of this UV treatment, the site could remain hazardous.  That’s why Norman Forsberg’s upcoming paper and Marc Elie’s work with ultra violet light in the Anderson laboratory (Project 4) is so interesting.

What still needs to be understood?  

The formation and concentration of these compounds in the environment at contaminated sites are poorly understood. It is important to continue three areas of research that have been going on at OSU.

  1. Detection: If the compounds are not present, then there’s less to worry about.

    Good times with lab mates when Steven O’Connell (right) first started working in the Anderson lab.
  2. Toxicity:  Addresses concerns over compounds that are detected in environmental samples.
  3. Processes by which OPAHs are made or degraded.

With that knowledge, it will become easier to understand potential risks with this compound class.

Why is this paper important in advancing the science?

My paper is very analytical.  If you watch the television series Bones, I would be most like Hodgins, except there would be less talk of “particulates” and more talk of cleaning instrumentation.  But seriously, by providing two methods on very different instrumentation to measure over 20 OPAHs, I provided a helpful platform for other scientists to use and build upon to measure this compound class in a variety of applications.

 

 

The OSU Superfund Center’s Community Engagement Core is fortunate to have an established partnership with the Confederated Tribes of the Umatilla Indian Reservation (CTUIR).

The recently produced CTUIR – OSU 2012-2013 Newsletter shares the background, summary, and findings of a collaborative research project to understand polycyclic aromatic hydrocarbon (PAH) exposure related to smoked salmon.

salmon
Salmon fillet

Salmon, a first food, is important to the subsistence of Native Americans living in the Pacific Northwest. Smoking salmon is one of the traditional ways to preserve this seasonally abundant food and make it available year round.

People can be exposed to PAHs from breathing contaminated air or eating smoked foods although many other exposure pathways exist.

Each volunteer wore air sampling equipment and turned it on every time they went into the smoking structures.

The data showed the air in the tipi and the smoke shed contained PAHs.

tipi        tipifire       smokehouse

Pictured above from left: Traditional tipi, volunteer tending the fire in the tipi wearing an air sampler in black bag on his hip, traditional smoke shed.

The findings from this study were published in the Journal of Agricultural & Food Chemistry.
B, Harris S, Matzke M, Cardenas A, Waters K, Anderson K. (2012). Effect of Native American fish smoking methods on dietary exposure to polycyclic aromatic hydrocarbons and possible risks to human health. Journal of Agricultural & Food Chemistry, 60(27), 6899-6906. doi: 10.1021/jf300978m

Indigenous cultures perceive the natural environment as an essential link between traditional cultural practices, social connectedness, identity, and health. Many tribal communities face substantial health disparities related to exposure to environmental hazards. We asked 27 volunteers who were members of the CTUIR their opinions on meanings of health and how their environment interacts with their health.

The findings from the focus group discussions were published in the journal Environmental Justice.

Schure M, Kile ML, Harding AK, Harper B, Harris S, Uesugi S, Goins T. Perceptions of environment and health among community members of the Confederated Tribes of the Umatilla Indian Reservation.  Environmental Justice. June 2013, 6(3): 115-120. doi:10.1089/env.2013.0022.

In addition, the CTUIR – OSU 2012-2013 Newsletter shares recently appointed members of the Tribal Advisory Board.

We hope you enjoy the newsletter!

ZebrafishRobert Tanguay, PhD (Project 3 ) focuses on examining the effects of selected chemicals and chemical classes on zebrafish development and associated gene expression pathways.

The Tanguay research group recently collaborated with Terrence J. Collins, PhD, a champion in the field of green chemistry at Carnegie Mellon University.

Collins and his collaborators showed that specific green chemicals (a group of molecules called TAML activators) used with hydrogen peroxide, can effectively remove steroid hormones from water after just one treatment. Steroid hormones are common endocrine disruptors found in almost 25 percent of streams, rivers, and lakes.  Collins needed to understand the safety of TAML activators to move forward on this problem.

Tanguay’s group exposed zebrafish embryos to seven different types of TAML activators. None of the TAML’s impaired embryo development at concentrations typically used for decontaminating water.

The collaboration resulted in a new journal publication in Green Chemistry.

These are important findings that contribute toward TAML activators getting commercialized for water treatment.

Endocrine disruptors and human health

Endocrine disruptors can disrupt normal functions of the endocrine system and impair development, by mimicking or blocking the activities of hormones in wildlife. Several animal studies suggest that endocrine disruptors can also affect human health, and may be involved in cancers, learning disabilities, obesity, and immune and reproductive system disorders.

Robert Tanguay’s leadership in utilizing  zebrafish

Robert Tanguay is Director of the Sinnhuber Aquatic Research Laboratory, which is the largest zebrafish toxicology lab in the world.

In 2012, Dr. Tanguay received an EPA grant award, “Toxicity Screening with Zebrafish Assay”.  The award is for three years and almost two million dollars in funding to examine the developmental toxicology of at least 1000 chemicals.

Dr. Tanguay and his research team  have tested over 3,000 compounds of interest to the National Toxicology Program (NTP), to complement the ongoing high-throughput screening efforts in the U.S. government’s multiagency Tox21 research program.

More Information:

Citation: Truong L, DeNardo MA, Kundu S, Collins TJ, Tanguay RL.  2013. Zebrafish assays as developmental toxicity indicators in the green design of TAML oxidation catalysts. Green Chem; doi:10.1039/C3GC40376A [Online 15 July 2013].