# The DNA adductome of lung carcinogenesis

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $351,684

## Abstract

SUMMARY
Lung cancer is the most common cancer worldwide, accounting for 1.6 million deaths in 2012 and for 158,000
deaths in the US in 2015. Despite the clear role of cigarette smoke in this epidemic, the precise mechanisms
through which this cancer develops remain unclear. Despite anti-smoking campaigns, in 2014 there were still 40
million smokers in the U.S. and over 1 billion worldwide. More effective strategies for prevention and treatment
of this disease, demand better tools to understand the mechanisms of lung cancer etiology and development.
Numerous studies have shown that chemicals present in tobacco smoke induce DNA modifications (DNA
adducts) which if not repaired, can lead to mutations ultimately resulting in loss of normal cellular growth control
mechanisms and lung cancer. Many of these studies, using relatively non-specific techniques such as
immunoassay and 32P-postlabelling, have clearly shown that DNA adduct levels are higher in the lungs of
smokers than non-smokers, which is consistent with the multiple mutations found in the lungs of smokers.
However, use of these non-specific techniques has not resulted in the positive structural characterization of any
DNA adduct, and thus on a clear identification of the mechanisms involved in their formation. Other studies
targeted at specific DNA adducts, have resulted in the identification of a few chemically characterized DNA
adducts, but these results do not explain those found using the more general non-specific approaches. A precise
characterization of the DNA damage during lung carcinogenesis that is both precise and comprehensive remains
elusive. We have developed a new mass spectrometry based DNA adductomic approach performing
comprehensive high resolution analysis of DNA adducts and providing information on their fragmentation
allowing for structural elucidation. Our long-term goal is to determine the DNA damage profile characterizing
lung carcinogenesis to identify a DNA adductome that may be ultimately used for early detection prevention and
treatment. Our hypothesis is that with our method will combine the screening ability of the non-specific methods
used in the past with the specific chemical characterization of the various modifications detected, resulting in a
specific adductomic profile. The objectives of this application are: 1. to characterize the lung DNA adductome in
animal models using the tobacco specific nitrosamine NNK to induce lung cancer and identify the driver adducts
by enhancing its effects by co-exposure to the pro-inflammatory agent lipopolysaccharide (LPS); 2. to
characterize the evolution of the DNA adductome in these models over time, clarifying the contribution of
inflammation and endogenous processes; 3. to characterize the DNA adductome in smokers' lung DNA
comparing it to non-smokers and to the profile identified in the animal models. Collectively our results will
characterize the adductome associated with NNK and NNK+LPS induced lung carcinogenesis...

## Key facts

- **NIH application ID:** 9897494
- **Project number:** 5R01CA220376-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Silvia Balbo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,684
- **Award type:** 5
- **Project period:** 2018-04-04 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897494

## Citation

> US National Institutes of Health, RePORTER application 9897494, The DNA adductome of lung carcinogenesis (5R01CA220376-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9897494. Licensed CC0.

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