# Cytosine Deamination Adducts and Cancer Etiology

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $414,693

## Abstract

!
ABSTRACT
DNA damage drives human genetic disease including cancer. Exogenous chemicals and endogenous reactive
molecules can damage DNA bases forming “adducts”. Unrepaired DNA adducts can block DNA synthesis or
miscode during polymerase-mediated replication. The landscape of mutations observed in human cancers is
dominated by C:G to T:A transition mutations. A major cause of these mutations is the hydrolytic deamination
of cytosine and cytosine analogs in DNA to their corresponding uracil analogs, generating a class of cytosine
deamination adducts, xU. Endogenous DNA adducts such as xU have proven more difficult to study due to the
similarity of these adducts to normal DNA constituents as well as their formation in normal, unperturbed cells
and tissues. In this application, we describe innovative new approaches that will allow definitive identification of
xU adducts in DNA using mass spectrometry methods. Further, we will measure the formation and repair of
such adducts at known cancer-driving mutational hotspots and genome-wide in both normal human cells and
cells with known repair defects. We will also examine xU in discard human tissues representing normal,
inflamed and diseased specimens. The studies proposed here will provide an unprecedented examination of
this important but understudied class of DNA adducts at the level of DNA sequence. The results of the
proposed studies could potentially result in clinically useful approaches to examine the damage history of a
given tissue, and provide an estimate as to how far the damage had progressed toward the development of
tumors. The anticipated results will shed new light on cancer etiology and potentially direct approaches to
reduce cancer incidence and provide earlier detection.
!
!

## Key facts

- **NIH application ID:** 9870902
- **Project number:** 5R01CA228085-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Lawrence C Sowers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $414,693
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870902

## Citation

> US National Institutes of Health, RePORTER application 9870902, Cytosine Deamination Adducts and Cancer Etiology (5R01CA228085-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9870902. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*