# High resolution mass spectrometric profile analysis of carcinogen-DNA adducts in oral cells of cigarette smokers and squamous cell carcinoma of the head and neck

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $641,384

## Abstract

Squamous cell carcinoma of the head and neck (HNSCC) is a devastating, frequently disfiguring, and often
fatal disease, expected to affect more than 53,000 people in the U.S. in 2020 and kill more than 10,000.
Prevention of this terrible disease is critical. Cigarette smoking, alcohol consumption, and human papilloma
virus (HPV) are well established major causes of HNSCC; only smoking and alcohol consumption are
considered here. Cigarette smoking and alcoholic drinks are sources of multiple DNA adducts that are critical
in the carcinogenic process. This proposal will establish a liquid chromatography-nanoelectrospray ionization-
high resolution tandem mass spectrometry (LC-NSI-HRMS/MS) profile analysis of 12 oral cell DNA adducts
that are likely causes of HNSCC. This was inspired by our recent analysis of DNA adducts in oral cells, in
which we found levels more than 20 times higher in cigarette smokers than in non-smokers. These exciting
results encouraged us to propose a profile analysis of important carcinogen-derived DNA adducts in oral cells
according to the following specific aims:
1. Develop an LC-NSI-HRMS/MS profile analysis method for quantitation of 12 important and representative
 carcinogen and toxicant – DNA adducts in human oral cells and tissue. The adducts are derived from
 various carcinogens and DNA reactive compounds in cigarette smoke and alcoholic beverages.
2. Apply the profile analysis to oral cells from currently healthy individuals: a) 100 non-smokers who are non-
 drinkers or light drinkers; b) 100 cigarette smokers who are non-drinkers or light drinkers; and c) 100
 cigarette smokers who are moderate or heavy drinkers. Comparisons of adduct levels in groups a and b
 will identify adducts enhanced by cigarette smoking while comparisons of groups b and c will identify
 adducts that are enhanced by the combination of smoking and moderate or heavy drinking.
3. Test the longitudinal stability of the oral cell DNA adduct profile analysis over a 6 month period in 50
 smokers who are non-drinkers or light drinkers.
4. A) Determine the DNA adduct profile in oral cells collected from 75 smokers with HNSCC and compare to
 that in 200 smokers without HNSCC recruited in Specific Aim 2 with the goal of identifying an adduct profile
 that is characteristic of HNSCC incidence.
 B) Compare the oral cell DNA adduct profile from part A of this aim to that in tissue, both normal and
 tumor, in a subset of 60 patients from part A who undergo surgery, to determine whether oral cell DNA
 adduct patterns are consistent with those in tissue.
Our results will potentially identify individuals who are susceptible to HNSCC but are unable to quit smoking.
Once identified, aggressive lifestyle and monitoring interventions in these subjects such as oral examinations
2-4 times per year can be initiated for prevention or early detection of this disfiguring and often fatal cancer.

## Key facts

- **NIH application ID:** 10275874
- **Project number:** 1R01CA263084-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** STEPHEN S HECHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $641,384
- **Award type:** 1
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275874

## Citation

> US National Institutes of Health, RePORTER application 10275874, High resolution mass spectrometric profile analysis of carcinogen-DNA adducts in oral cells of cigarette smokers and squamous cell carcinoma of the head and neck (1R01CA263084-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10275874. Licensed CC0.

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