# Core 3 - Biomarkers and Product Evaluation

> **NIH NIH P01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $199,561

## Abstract

ABSTRACT – CORE 003: Biomarkers and Product Evaluation Core
The goal of the Biomarkers and Product Evaluation Core is to facilitate the research proposed in Project
MARVEL by providing data on biomarkers of exposure and biological effects as well as to characterize
commonly used vaping products. These data will allow individual projects to achieve their Specific Aims. The
measurement of toxicant and carcinogen metabolites in body fluids of people who use tobacco products is the
accepted method for objective assessment of exposure to these products. Total nicotine equivalents (TNE),
the sum of nicotine and six nicotine metabolites accounts for >85% of the nicotine dose, is a well-established
biomarker of nicotine exposure. The primary pathway of nicotine metabolism is cytochrome P450 2A6
(CYP2A6)-catalyzed C-oxidation, which leads to the formation of cotinine. Cotinine is further metabolized, also
by CYP2A6, to 3'-hydroxycotinine. The ratio of 3'-hydroxycotinine to cotinine in plasma or saliva (referred to as
the NMR) is an excellent phenotypic measure of CYP2A6 activity, and may be used to characterize individual
differences in nicotine metabolism. Urinary concentrations of the acrylonitrile mercapturic acid, 2-cyanoethyl-
mercapturic acid (CEMA) is from 100 to more than 400 times higher in smokers compared to non-smokers and
can be used to distinguish combustible from non-combustible tobacco use with sensitivity and specificity
>99%. The mercapturic acids of acrolein, crotonaldehyde, and benzene, 3-hydroxypropyl-mercapturic acid
(3HPMA), 3-hydroxy-1-methylpropylmercpturic acid (HMPMA), S-phenylmercapturic acid (SPMA) can be used
to quantify exposure to volatile toxicants in cigarette and e-cigarette users. Oxidative damage can be
measured with urinary 8-iso-PGF2α, an F2-isoprostane and elevated PGE-M, a prostaglandin-E2 metabolite is
a biomarker of inflammation. Vaping products may vary widely in their fluid constituents and generated aerosol.
The Core will analyze saliva samples from Lab Study participants for cotinine and the NMR. Urine samples
from participants attending lab-based assessments will be analyzed for TNE, mercapturic acids, 8-iso-PGF2α
and .PGE-M. The Core will also determine e-liquid constituents and generated aerosol yield of the most
abundantly used e-cigarettes among the participants of this study. The Specific Aims are to: 1) Characterize
individual differences in nicotine metabolism and exposure in participants in the cohort study; 2) Quantify
exposure to other constituents found in tobacco products and systemic indices of oxidative stress and
inflammation in participants of the lab-based assessments; 3) Characterize toxic constituents in e-liquids and
aerosol. The Core is housed at the University of Minnesota which provides state-of-the-art expertise and
technology for the quantitation of these biomarkers, and the constituents of e-cigarettes. The University of
Minnesota is widely recognized as one of the leading academic ...

## Key facts

- **NIH application ID:** 10836424
- **Project number:** 5P01CA269048-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** SHARON E MURPHY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $199,561
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836424

## Citation

> US National Institutes of Health, RePORTER application 10836424, Core 3 - Biomarkers and Product Evaluation (5P01CA269048-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10836424. Licensed CC0.

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