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

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

• Shorey LE, Castro DJ, Baird WM, Siddens LK, Löhr CV, Matzke MM, Waters KM, Corley RA, Williams DE. Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): Timing of maternal exposures determines target tissue response in offspring. Cancer Lett. 2012 Apr 1;317(1):49-55. Epub 2011 Nov 13.  PubMed PMID: 22085489; PubMed Central PMCID: PMC3269513.
• Crowell SR, Sharma AK, Amin S, Soelberg JJ, Sadler NC, Wright AT, Baird WM, Williams DE, Corley RA. Impact of Pregnancy on the Pharmacokinetics of Dibenzo[def,p]chrysene in Mice.  Toxicol Sci. 2013 Sep;135(1):48-62. doi: 10.1093/toxsci/kft124. Epub 2013 Jun 6. PubMed PMID: 23744095

From LLNL

• Ultra-high efficiency moving wire combustion interface for on-line coupling of HPLC