Polyphenols from persimmon fruit attenuate acetaldehyde-induced DNA double-strand breaks by scavenging acetaldehyde

• Published in: Scientific reports 2022-06, Vol.12 (1), p.10300-10300, Article 10300
• Main Authors: Matsuzaki, Kenichiro, Kumatoriya, Kenji, Tando, Mizuki, Kometani, Takashi, Shinohara, Miki
• Format: Article
• Language: English
• Subjects: 631/337/1427; 631/337/1427/1979; 631/337/1427/2122; 631/337/1427/2190; 631/337/1427/2191; 631/337/1427/2566; Acetaldehyde; Acetaldehyde - toxicity; Alcohol use; Aldehyde dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial - metabolism; Carcinogenesis; Deoxyribonucleic acid; Diospyros; DNA; DNA Adducts; DNA Breaks, Double-Stranded; DNA damage; DNA End-Joining Repair; DNA Repair; Double-strand break repair; Ethanol; Fruit - metabolism; Fruits; Genomes; Genomic instability; Homology; Humanities and Social Sciences; Humans; Immunofluorescence; multidisciplinary; Non-homologous end joining; Polyphenols; Polyphenols - pharmacology; Risk reduction; Science; Science (multidisciplinary); siRNA; Yeast
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-14374-9

Acetaldehyde, a metabolic product of ethanol, induces DNA damage and genome instability. Accumulation of acetaldehyde due to alcohol consumption or aldehyde dehydrogenase ( ALDH2 ) deficiency increases the risks of various types of cancers, including esophageal cancer. Although acetaldehyde chemically induces DNA adducts, the repair process of the lesions remains unclear. To investigate the mechanism of repair of acetaldehyde-induced DNA damage, we determined the repair pathway using siRNA knockdown and immunofluorescence assays of repair factors. Herein, we report that acetaldehyde induces DNA double-strand breaks (DSBs) in human U2OS cells and that both DSB repair pathways, non-homologous end-joining (NHEJ) and homology-directed repair (HDR), are required for the repair of acetaldehyde-induced DNA damage. Our findings suggest that acetaldehyde-induced DNA adducts are converted into DSBs and repaired via NHEJ or HDR in human cells. To reduce the risk of acetaldehyde-associated carcinogenesis, we investigated potential strategies of reducing acetaldehyde-induced DNA damage. We report that polyphenols extracted from persimmon fruits and epigallocatechin, a major component of persimmon polyphenols, attenuate acetaldehyde-induced DNA damage without affecting the repair kinetics. The data suggest that persimmon polyphenols suppress DSB formation by scavenging acetaldehyde. Persimmon polyphenols can potentially inhibit carcinogenesis following alcohol consumption.