# Role of Aflatoxin-induced DNA Damage Formation and Repair in Hepatic Mutagenesis

> **NIH NIH R00** · UNIVERSITY OF GEORGIA · 2020 · $249,000

## Abstract

ABSTRACT / PROJECT SUMMARY
 Aflatoxin, produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is a well-known
environmental carcinogen that causes mutations and ultimately leads to hepatocellular carcinoma (HCC), one
of the leading causes of cancer deaths worldwide. Chronic dietary exposure to aflatoxin B1 (AFB1), the most
mutagenic aflatoxin, and chronic infections with the hepatitis B virus (HBV) or hepatitis C virus (HCV) are the
two major etiological factors for the development of HCC. Nucleotide excision repair is the repair mechanism
by which the bulky lesions induced by AFB1 are removed from the genome. Despite the progress in our
knowledge of the AFB1-DNA adduct, the formation and removal kinetics of the bulky DNA lesion throughout
the genome and the factors affecting the damage formation and repair efficiency remain elusive. Our long-term
goal of this project is to better understand how the kinetics of AFB1-induced DNA damage formation and repair
contributes to human hepatic mutagenesis. The overall objective of this particular proposal, which is an initial
step to achieve our long-term goal, is to combine biochemistry, genetics, adductomics and computational
approaches to investigate effects of histone modifications and three-dimensional (3D) genome organization on
AFB1-induced DNA damage formation and repair, and to determine the correlations between AFB1-DNA
adduct spectra or repair efficiencies and mutational spectra of AFB1 in human HCC. Our central hypothesis is
that human hepatic mutagenesis correlates with the AFB1-induced DNA damage formation and/or repair
events, which are affected by histone modifications and 3D genome organization. We propose two specific
aims to test our hypothesis and accomplish the objective: 1)! Genome-wide Analysis of AFB1-induced DNA
Damage Formation and Repair Kinetics as a Function of Histone Modifications and 3D Genome Organization
(Aim1, K99 and R00 phase). 2) Determine the Correlations Between AFB1-DNA Adduct Spectra or Repair
Efficiencies and Mutational Spectra of AFB1 in Human HCC (Aim2, R00 phase). We expect the following
outcomes: Determination of the effect of histone acetylation on AFB1-DNA adducts formation and repair
efficiency; determination of the effect of 3D genome organization on AFB1-DNA adducts formation and repair
efficiency; identification of AFB1-induced DNA damage hot spots and repair cold spots in cancer-associated
genes; determination of the correlations between AFB1-DNA adduct spectra or repair efficiencies and
mutational spectra of AFB1 in human HCC. The proposed research is significant because it will give insights
into development of AFB1-associated HCC, improve prevention strategies and develop better treatment for
HCC.

## Key facts

- **NIH application ID:** 10011805
- **Project number:** 4R00ES030015-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Wentao Li
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-09-03 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011805

## Citation

> US National Institutes of Health, RePORTER application 10011805, Role of Aflatoxin-induced DNA Damage Formation and Repair in Hepatic Mutagenesis (4R00ES030015-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10011805. Licensed CC0.

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