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,, on Twitter @OregonStateExt
Source: Susan Tilton, 541-737-1740,

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.

Erin Madeen, Project 1 Trainee

Congratulations to Erin Madeen from Project 1, the first recipient of a Trainee-Initiated Collaboration (TrIC) grant.

Erin will receive $2500 for travel and lodging to work with Ulrike Luderer MD, PhD, a Reproductive Toxicologist and expert in polycyclic aromatic hydrocarbon (PAH) Benzo(a)pyrene (BaP) induced female infertility at UC Irvine.

Dr. Luderer will train Erin on methods to histologically analyze ovaries and testes from mice treated prenatally with the PAH, dibenzo[def,p]chrysene (DBC), in a Project 1 study. This unique training opportunity will help further research exploring how exposure of pregnant mothers to PAHs induces reproductive effects in their offspring.

This area of research is valuable as several individual PAHs are well documented to cause reproductive effects that include abnormal morphology, reduced fertility, infertility, and cancers. DBC has not previously been studied as a reproductive toxicant.

A comparison of BaP and DBC reproductive effects could be useful for risk assessors and modelers as PAHs occur in dynamic mixtures.

This is an exciting new collaboration with the Luderer Lab.

OSU Press Release:

MEDIA CONTACT:  David Stauth, 541-737-0787

David Williams, 541-737-3277 or


CORVALLIS, Ore. – Researchers for the first time have developed a method to track through the human body the movement of polycyclic aromatic hydrocarbons, or PAHs, as extraordinarily tiny amounts of these potential carcinogens are biologically processed and eliminated.

PAHs, which are the product of the incomplete combustion of carbon, have been a part of everyday human life since cave dwellers first roasted meat on an open fire. More sophisticated forms of exposure now range from smoked cheese to automobile air pollution, cigarettes, a ham sandwich and public drinking water. PAHs are part of the food we eat, the air we breathe and the water we drink.

However, these same compounds have gained increasing interest and scientific study in recent years due to their role as carcinogens. PAHs or PAH mixtures have been named as three of the top 10 chemicals of concern by the Agency for Toxic Substances Disease Registry.

With this new technology, scientists have an opportunity to study, in a way never before possible, potential cancer-causing compounds as they move through the human body. The findings were just published by researchers from Oregon State University and other institutions in Chemical Research in Toxicology, in work supported by the National Institute of Environmental Health Sciences (NIEHS)

The pioneering work has been the focus of Ph.D. research by Erin Madeen at Oregon State, whose studies were supported in part by an award from the Superfund Research Program at NIEHS for her work at Lawrence Livermore National Laboratory.

“We’ve proven that this technology will work, and it’s going to change the way we’re able to study carcinogenic PAHs,” said David Williams, director of the Superfund Research Program at OSU, a professor in the College of Agricultural Sciences and principal investigator with the Linus Pauling Institute.

“Almost everything we know so far about PAH toxicity is based on giving animals high doses of the compounds and then seeing what happens,” Williams said. “No one before this has ever been able to study these probable carcinogens at normal dietary levels and then see how they move through the body and are changed by various biological processes.”

The technology allowing this to happen is a new application of accelerator mass spectrometry, which as a biological tracking tool is extraordinarily more sensitive than something like radioactivity measuring. Scientists can measure PAH levels in blood down to infinitesimal ratios – comparable to a single drop of water in 4,000 Olympic swimming pools, or to a one-inch increment on a 3-billion mile measuring tape.

As a result, microdoses of a compound, even less than one might find in a normal diet or environmental exposure, can be traced as they are processed by humans. The implications are profound.

“Knowing how people metabolize PAHs may verify a number of animal and cell studies, as well as provide a better understanding of how PAHs work, identifying their mechanism or mechanisms of action,” said Bill Suk, director of the NIEHS Superfund Research Program.

One PAH compound studied in this research, dibenzo (def,p)-chrysene, is fairly potent and defined as a probable human carcinogen. It was administered to volunteers in the study in a capsule equivalent to the level of PAH found in a 5-ounce serving of smoked meat, which provided about 28 percent of the average daily dietary PAH intake. There was a fairly rapid takeup of the compound, reaching a peak metabolic level within about two hours, and then rapid elimination. The researchers were able to study not only the parent compound but also individual metabolites as it was changed.

“Part of what’s so interesting is that we’re able to administer possible carcinogens to people in scientific research and then study the results,” Williams said. “By conventional scientific ethics, that simply would not be allowed. But from a different perspective, we’re not giving these people toxins, we’re giving them dinner. That’s how much PAHs are a part of our everyday lives, and for once we’re able to study these compounds at normal levels of human exposure.”

What a scientist might see as a carcinogen, in other words, is what most of us would see as a nice grilled steak. There are many unexpected forms of PAH exposure. The compounds are found in polluted air, cigarettes, and smoked food, of course, but also in cereal grains, potatoes and at surprisingly high levels in leafy green vegetables.

“It’s clear from our research that PAHs can be toxic, but it’s also clear that there’s more to the equation than just the source of the PAH,” Williams said. “We get most of the more toxic PAHs from our food, rather than inhalation. And some fairly high doses can come from foods like leafy vegetables that we know to be healthy. That’s why we need a better understanding of what’s going on in the human body as these compounds are processed.”

The Williams-led OSU laboratory is recruiting volunteers for a follow-up study that will also employ smoked salmon as a source of a PAH mixture and relate results to an individual’s genetic makeup.

Some of the early findings from the study actually back up previous research fairly well, Williams said, which was done with high-dose studies in laboratory animals. It’s possible, he said, that exposure to dietary PAHs over a lifetime may turn out to be less of a health risk that previously believed at normal levels of exposure, but more work will need to be done with this technology before such conclusions could be reached.

Collaborators on the study were from the Pacific Northwest National Laboratory, Lawrence Livermore National Laboratory, and the OSU Environmental Health Sciences Center.

“Further development and application of this technology could have a major impact in the arena of human environmental health,” the researchers wrote in their conclusion.

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Hi, my name is Tod (with one “d”) Harper Jr, and I am recent transplant to Corvallis from Galveston, Texas.

While in Texas I earned a B.S. in Marine Biology from Texas A&M University @ Galveston and a PhD. in Pharmacology & Toxicology from The University of Texas Medical Branch. My dissertation project in the laboratory of Dr. Cornelis Elferink focused on identifying physiological functions of the aryl hydrocarbon receptor.

Tod enjoying his lobster!
Tod enjoying his lobster!

As a postdoctoral fellow at Oregon State University in Dr. David William’s laboratory (Project 1),  I am investigating the early mechanisms involved in cancer initiation after in utero exposure to the environmental contaminants. In addition, I am investigating how maternal consumption of dietary phytochemicals can protect the developing fetus from environmental insults in the womb.

When I am not in the laboratory I can most likely be found camping, trail running, eating oysters by the dozen, and/or enjoying one of Oregon’s fine craft brews!


By Erin Madeen, Ph.D. candidate and Project 1 Trainee

Erin Madeen working at the Lawrence Livermore National Laboratory.
Erin Madeen working at the Lawrence Livermore National Laboratory.

Using new technology at Lawrence Livermore National Laboratory (LLNL), Oregon State University researchers are able to perform a controlled study of the human metabolism of environmental contaminate PAHs for the first time.

The Williams Laboratory has studied PAHs (polycyclic aromatic hydrocarbons) for over a decade, traditionally relying on animal and in vitro models of metabolism and toxicity. PAHs are produced by the burning of carbon-containing materials, for example forest fires, charcoal grilling, and engine combustion. After production, PAHs cling to foods such as vegetables, cereal grains, or smoked meats. Some of these compounds cause cancer at high doses in animal models.

As a graduate student in the Williams Lab, one of my projects is to relate PAH data to human health.  With our partners at LLNL, a sensitive tool known as an AMS (accelerator mass spectrometer) is used to detect very small doses of PAHs in urine or blood plasma.  We gave a model PAH called DBC [Dibenzo (def,p) chrysene] to human volunteers in doses less than what can be found in a charbroiled burger. This research has not been possible until now because of potential toxicity risks.  Traditional non-AMS methods need a larger dose of DBC which could pose too high of a risk to study participants.

With the support of LLNL staff and the OSU Superfund Research Program, I received a K.C. Donnelly Externship Supplement through the NIEHS Superfund Research Program.  This award supported my travel to LLNL for this project. My experience at LLNL greatly solidified my understanding of and appreciation for AMS. Maintaining and continuously developing unique instrumentation, such as AMS, requires a highly specialized, dedicated, and flexible team.  The environment of a national laboratory is different from that of university research.  Most notably this difference is in the concentration of specialists in a particular field and the team approach to problem solving. It was humbling to observe the amount of time, resources, and effort that the LLNL AMS staff dedicated to training and to progress on our DBC project. This externship allowed me to experience being part of the AMS team and to process my own samples, providing valuable insight that will help guide further work on our projects.

Accelerator Mass Spectrometry (AMS) is an instrument traditionally used for carbon dating. It has been modified to detect stable isotopes in biological samples. The AMS at LLNL is unique because it is able to use liquid samples.  The liquid biological samples are separated according to the changes the body makes to DBC, known as DBC metabolites.  The carbon isotope added to the DBC chemical structure was used to identify several different metabolites in human urine and plasma.  This project is ongoing as we continue to develop a profile of the human metabolism of DBC over time.

Related journal publications:

From OSU Superfund Research Program