# Elucidating Metabolic and Physicochemical Mechanisms of PAH Susceptibility in Toxicity Test Systems and Humans

> **NIH NIH P42** · OREGON STATE UNIVERSITY · 2022 · $330,403

## Abstract

PROJECT SUMMARY – TEEGUARDEN PROJECT
Lack of understanding the molecular basis for susceptibility across toxicity test systems is a long-standing
barrier to improved risk assessment, improved cleanup decisions for SRP sites, and successful health
mitigations. Our objective is to develop transformative, activity-based proteomic probes and multi-modal
chemical microscopy to measure the metabolic and distributional processes that contribute to differential
susceptibility to PAH exposure. We hypothesize that measurable but commonly ignored differences in tissue
distribution and metabolic capacity to activate and/or detoxify PAHs contributes to differential susceptibility.
To test our hypothesis, we will complete three aims: 1. Identify the complete set of active P450, glutathione-S-
transferase and UDP-glucuronosyltransferase enzymes that metabolize PAHs & PAH metabolites. We will
incubate activity-based probes in tissue samples to enrich and identify active enzymes using our proteomics
platform. 2. Develop a single assay to determine both PAH metabolic rates and metabolic susceptibility by
relating PAH metabolic rates to global measures of enzyme activity. We will incubate activity-based probes in
tissues while conducting standard PAH metabolism assays to determine substrate specificity and metabolic
constants for active enzymes. 3. Determine how exposure susceptibility across test systems and humans
depends upon PAH physicochemical properties, tissue composition, and body composition. We will measure
tissue composition across our systems and measure and predict the disposition of PAHs across these systems,
and humans. The products of our research directly enhance the relevance and impact of each project and core
for stakeholders. Our innovations (ABPP and multi-modal chemical microscopy) will open new scientific
horizons in the understanding of two key molecular determinants of differential susceptibility. The work will
satisfy explicit expectations for SRP by a) demonstrating “that the hazardous substance, its dose, exposure
pathway and model organisms are considered within the context of timing, prevalence, and detection of
exposure” and by b) assuring that the “work is contextualized in terms of its relevance to human exposure.”
Our research results will directly inform and improve human health assessment for PAHs at Superfund sites.

## Key facts

- **NIH application ID:** 10339461
- **Project number:** 5P42ES016465-13
- **Recipient organization:** OREGON STATE UNIVERSITY
- **Principal Investigator:** Justin Gary Teeguarden
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $330,403
- **Award type:** 5
- **Project period:** 2009-09-17 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10339461

## Citation

> US National Institutes of Health, RePORTER application 10339461, Elucidating Metabolic and Physicochemical Mechanisms of PAH Susceptibility in Toxicity Test Systems and Humans (5P42ES016465-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10339461. Licensed CC0.

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