Mechanisms of PAH Susceptibility

What We Do

In our project, we aim to understand how humans metabolize PAHs. Specialized proteins called enzymes break down PAHs in the body. Some PAH metabolic products are harmless and are rapidly eliminated, but some PAH metabolites can cause health problems like cancer. As such, we measure rates of PAH metabolism in tissues and organs, and integrate those measurements into computational models that allow us to predict internal concentrations of PAHs or PAH metabolites in the body from an oral or inhalation exposure. These models can be used to determine what exposures can lead to toxic levels inside the body.

Our project asks the following questions

Which enzymes metabolize PAHs?

We use activity-based protein profiling to identify which enzymes metabolize different PAHs. We then determine the prevalence (frequency) of these enzymes in the human population.

What are the rates of PAH metabolism in human tissues?

The goal of this work is to identify the rate at which different PAHs are metabolized by different enzymes. We can do this using in vitro tests to identify the rate of metabolism. Then, we can look at how the rates change based on the enzyme being used.

Can computational models be used to predict internal concentrations of PAHs?

As we identify rates of PAH metabolism, we can use these rates to build a computer model. We can add in the prevalence of these enzymes in the human population to better understand how PAH metabolism rates may change between people (intra-individual variability) and how they may change based on the exposure and dose.

Collaborations

Through work with the Predicting the Toxicity of Complex PAH Mixtures project, we are assessing how retene is metabolized in the human body.
We work with the PAH Fate and Exposure, PAH Remediation and Transformations, and Predicting the Toxicity of Complex PAH Mixtures projects and the Chemical Mixtures Core to obtain PAHs and mixtures found in the environment, and evaluate the toxicity of each PAH, PAH mixture, and subsequent metabolites using zebrafish screening. The proven advantages of the zebrafish model can provide the relative toxicity of real-world mixtures from Superfund sites in just a few days. Additionally, the zebrafish data are used to guide cleanup efforts at contaminated sites to better protect human health and the environment.
We are working with the Predicting the Toxicity of Complex PAH Mixtures and PAH Health Outcomes projects to develop models of zebrafish and human 3D lung cells to predict PAH concentrations in those models.
Through our work with the PAH Fate and Exposure and PAH Remediation and Transformations projects, we are prioritizing which PAHs and PAH mixtures to assess.

Contact Info

The Superfund Research Center