# Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells

> **NIH NIH R03** · UNIVERSITY OF MINNESOTA · 2022 · $77,500

## Abstract

Project Summary
Cigarette smoking is the leading cause of lung and oral cancer in the United States. Smokeless tobacco causes
cancer of the mouth, esophagus and pancreas. The health effects of e-cigarettes are still under investigation but
may disturb oral cavity homeostasis and cause lung and cardiovascular diseases. The tobacco-specific
nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are
classified as human carcinogens by the International Agency for Research on Cancer, and are recognized
causes of these diseases. Metabolic activation of NNK and NNN results in formation of reactive electrophiles
that modify DNA to produce a variety of products such as N7-[4-(3-pyridyl)-4-oxobut-1-yl]-deoxyguanosine
(N7POBdG) that can result in apurinic/apyrimidinic (AP) sites in DNA by facile hydrolysis of the base-
deoxyribonucleoside bond; other tobacco constituents may also induce AP sites. AP site accumulation may
initiate the carcinogenic process. Oral cells provide the direct link between tobacco use and oral cancer in
humans and elevated DNA damage has been found in oral cells of tobacco users. We propose to analyze AP
sites in oral cell DNA with two specific aims: to develop a highly sensitive mass spectrometric method to quantify
AP sites in human oral cell DNA, and to quantify AP sites in oral cell DNA induced by cigarette smoke, smokeless
tobacco and e-cigarettes. The goals are to establish oral cell DNA AP sites as biomarkers of tobacco induced
DNA damage in cigarette smokers, smokeless tobacco users, and e-cigarette users, and to ultimately identify
susceptible tobacco users and design effective strategies to prevent cancer. This study may also provide
preliminary data for a large epidemiologic study. We have strong preliminary data to support this proposal.

## Key facts

- **NIH application ID:** 10359388
- **Project number:** 1R03CA259652-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Jiehong Guo
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,500
- **Award type:** 1
- **Project period:** 2022-01-31 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359388

## Citation

> US National Institutes of Health, RePORTER application 10359388, Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells (1R03CA259652-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10359388. Licensed CC0.

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