# Chemoprevention by Black Raspberry of Oral Cancer Induced by Tobacco Carcinogens: Translational Studies

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $344,294

## Abstract

Project Abstract
Tobacco use remains a high risk factor for oral squamous cell carcinoma (OSCC) resulting from exposure to
potent tobacco carcinogens including polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[a,l]pyrene
(DB[a,l]P), benzo[a]pyrene (B[a]P) and tobacco-specific nitrosamines (TSNA) such as N’-nitrosonornicotine
(NNN). To assess effects of these carcinogens on oral mucosa, we developed a novel OSCC mouse model
using DB[a,l]P and its fjord region diol epoxide (DB[a,l]PDE). Importantly, we showed that dietary intervention
with freeze-dried black raspberries (BRB) powder inhibited carcinogen-induced DNA damage, mutagenesis and
carcinogenesis in the mouse oral cavity. We have also established that BRB reduce formation and/or enhance
repair of bulky adducts in vitro, but, the mechanisms by which BRB reduce DNA damage remain to be fully
elucidated. Considering the varied structures of DNA adducts, we will focus on BRB effects on the nucleotide
excision repair (NER) and base-excision repair (BER) enzymes. Based on the abundant phenolic compounds
in BRB e.g. anthocyanins, it is logical to propose that BRB help preserve the cellular redox poise, enhance redox
scavenging and thus function to prevent oxidative DNA damage; our data support this proposition. In addition
to their cytoprotective functions, a specific cellular reducing equivalent-NADPH-functions in reductive
biosynthetic reactions including conversion of ribonucleotides to deoxyribonucleotides (dNTPs) that are essential
components for DNA repair. Based on these data, we hypothesize that BRB reduce DNA damage (cf.
Scheme 1, Significance) in a multimodal fashion: 1) BRB enhance NER and BER function via preservation
of key substrates and cofactors i.e. dNTPs and Mg2+, while maintaining an optimal, non-oxidized environment
conducive to DNA repair; 2) BRB preserve the cellular redox status via efficient scavenging of reactive species
that can inhibit DNA repair enzymes thereby reducing oxidative DNA damage. The proposed mechanistic
studies entail two complementary, yet independent, Specific Aims: Aim 1A will investigate the effects of BRB
on repair (NER, BER) of covalent tobacco carcinogen-DNA adducts and 8-OXO-dG in primary human
oral keratinocyte cells that have been transfected with these adducts using our established assay. Aim
1B will determine the capacity of BRB to prevent oxidative damage in wild-type (OGG1+/+, a component
of BER enzymes) and knockout (OGG1-/-) MEF cells. Concurrent studies, applicable to both subaims, will
assess BRB effect on preservation of dNTP pools and key cellular redox poise parameters in a continuum of
validated cells ranging from primary human oral keratinocytes, oral leukoplakia and OSCC cells. Aim 2 will
determine for the first time the effects of local BRB delivery on formation of covalent DNA adducts and
8-OXO-dG in buccal cells of healthy smokers. The results could serve as the framework for future
chemopreventive trials for addicted smokers ...

## Key facts

- **NIH application ID:** 9885149
- **Project number:** 2R01CA173465-06A1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** KARAM E EL-BAYOUMY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,294
- **Award type:** 2
- **Project period:** 2013-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9885149

## Citation

> US National Institutes of Health, RePORTER application 9885149, Chemoprevention by Black Raspberry of Oral Cancer Induced by Tobacco Carcinogens: Translational Studies (2R01CA173465-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9885149. Licensed CC0.

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