# Ethanol-induced skin changes

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $184,656

## Abstract

PROJECT SUMMARY/ABSTRACT
The incidence of most cancers has declined, but that of melanoma continues to rise. About 200,000 new
cases of melanoma will be diagnosed in 2020. Although one major risk
ultraviolet (UV) exposure, not all forms of melanoma are related to sun
factor linked to melanoma incidence is
exposure or occur in sun-exposed
areas. A better understanding of UV-unrelated risk factors will help in developing more effective preventative
strategies for melanoma. Recent studies, including ours, have shown that alcohol consumption is positively
linked to an increased risk of melanoma. However, no studies have tested this connection and elucidated the
mechanisms in vitro and in vivo.
 Alcohol is first metabolized to acetaldehyde (AcAH) by alcohol dehydrogenase (ADH), and then oxidized to
acetic acid by mitochondrial aldehyde dehydrogenase 2 (ALDH2). Alongside these two major enzymes,
another enzyme, cytochrome p450 2E1 (CYP2E1), is involved in the conversion of alcohol to AcAH and then to
acetic acid. To understand the relation between alcohol-metabolizing enzymes and melanoma, we used The
Cancer Genome Atlas (TCGA) database and analyzed ADH (1A, 1B and 1C), ALDH2 and CYP2E1. We found
a strong correlation between low expression of ALDH2 mRNAs and worse prognosis of melanoma patients.
ALDH2 could be inactivated by many environmental factors. To understand the role for ethanol and inactivated
ALDH2 in skin biology, we used ten-week-old Aldh2 KO mice. Because carcinogenesis is a chronic process,
we used a mouse model of chronic alcohol consumption, where 3-5% and 10% (v/v) ethanol was provided as
sole drinking fluid. Our preliminary experiments revealed a unique DNA damage pattern and melanocyte
proliferation by ethanol in Aldh2 KO mice. In this grant application, we hypothesize that ethanol and/or AcAH
induce cellular stress responses leading to melanocyte activation and dark CPD formation, and propose to
define transcriptomes associated with ethanol-induced skin changes in mice (Aim 1) and the mechanisms of
dark CPD formation by ethanol/AcAH in melanocytes (Aim 2).
 The effect of ethanol and/or acetaldehyde on skin changes has yet to be studied. Given the unique DNA
damage induced by UV, our findings that ethanol induces melanocyte proliferation and UV-induced DNA
damage without UV exposure warrant further phenotypic, functional and mechanistic studies, which will be
further explored in future R01 applications.

## Key facts

- **NIH application ID:** 10478153
- **Project number:** 5R21AA028904-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Mayumi Fujita
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $184,656
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478153

## Citation

> US National Institutes of Health, RePORTER application 10478153, Ethanol-induced skin changes (5R21AA028904-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10478153. Licensed CC0.

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