Investigations on the new mechanism of action for acetaldehyde-induced clastogenic effects in human lung fibroblasts

Hande, Varsha; Teo, K.; Srikanth, Prarthana; Wong, Jane; Sethu, Swaminathan; Lopez, Wilner Martinez; Hande, Manoor Prakash

doi:10.1016/j.mrgentox.2020.503303

Cited by 7 publications

(7 citation statements)

References 75 publications

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“…2 f and S2a ). Consistent with a previous report 22 , 33 , our observations indicate that acetaldehyde can induce DSBs in vivo and suggest that HR and NHEJ are involved in the repair of acetaldehyde-induced DSBs. Considering acetaldehyde is a highly reactive molecule, our observations prompted us to test whether acetaldehyde chemically cleaves the DNA directly.…”

Section: Resultssupporting

confidence: 93%

“…RAD51 accumulates at stalled replication forks and DNA DSBs 19 , 32 , suggesting that acetaldehyde leads to replication fork stalling or DSB formation. Previous reports have demonstrated that γH2AX focus formation increases after acetaldehyde treatment 33 . γH2AX focus formation is caused by DSB formation or replication fork stalling without breaks (e.g.…”

Section: Resultsmentioning

confidence: 88%

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

Matsuzaki

Kumatoriya

Tando

et al. 2022

Sci Rep

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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.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 88%

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

Matsuzaki

Kumatoriya

Tando

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Another DNA adduct, 1,N 2 -propano-2'-deoxyguanosine (PdG), can also be generated from acetaldehyde in the presence of histones and other basic compounds. PdG is responsible for genotoxic and mutagenic effects [ 34 ]. In vitro studies show that acetaldehyde induces clastogenic effects, as evidenced by the increase in micronuclei frequency, DNA breaks, the cell growth cycle stopping at the G2/M phase, and the decrease of cell vitality [ 33 , 34 ].…”

Section: Ethanol Metabolism and Its Consequencesmentioning

confidence: 99%

Alcohol and breast cancer

2022

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Breast cancer is one of the main causes of death in women worldwide. In women, breast cancer includes over half of all tumours caused by alcohol. This paper discusses both ethanol metabolism and the mechanisms of mammary tumourigenesis caused by alcohol. Numerous signalling pathways in neoplastic transformation following alcohol consumption in women have been presented. In addition, primary and secondary prevention, phytochemicals, synthetic chemicals, specific inhibitors of enzymes and selective receptor modulators have been described.

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“…Acetaldehyde may form DNA adducts that impair proper DNA function if not eliminated or repaired [ 68 , 69 , 70 ] ( Figure 2 ). In vitro studies with human lung fibroblasts indicated that acetaldehyde induces clastogenic effects with detected DNA breaks at telomeric regions, arresting cells at the G2/M phase and negatively affecting cell viability [ 71 ]. The increase in acetate units resulting from ethanol’s active oxidative metabolism, accompanied by food intake restriction, depleted glycogen reserves, and increased NADH concentrations, favors ketone bodies’ synthesis from acetate.…”

Section: Ethanol Induces Metabolic Alterations That May Cause or Facilitate Cancer Developmentmentioning

confidence: 99%

Biochemical Mechanisms Associating Alcohol Use Disorders with Cancers

Rodríguez

Coveñas

2021

Cancers

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The World Health Organization identifies alcohol as a cause of several neoplasias of the oropharynx cavity, esophagus, gastrointestinal tract, larynx, liver, or female breast. We review ethanol’s nonoxidative and oxidative metabolism and one-carbon metabolism that encompasses both redox and transfer reactions that influence crucial cell proliferation machinery. Ethanol favors the uncontrolled production and action of free radicals, which interfere with the maintenance of essential cellular functions. We focus on the generation of protein, DNA, and lipid adducts that interfere with the cellular processes related to growth and differentiation. Ethanol’s effects on stem cells, which are responsible for building and repairing tissues, are reviewed. Cancer stem cells (CSCs) of different origins suffer disturbances related to the expression of cell surface markers, enzymes, and transcription factors after ethanol exposure with the consequent dysregulation of mechanisms related to cancer metastasis or resistance to treatments. Our analysis aims to underline and discuss potential targets that show more sensitivity to ethanol’s action and identify specific metabolic routes and metabolic realms that may be corrected to recover metabolic homeostasis after pharmacological intervention. Specifically, research should pay attention to re-establishing metabolic fluxes by fine-tuning the functioning of specific pathways related to one-carbon metabolism and antioxidant processes.

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Investigations on the new mechanism of action for acetaldehyde-induced clastogenic effects in human lung fibroblasts

Cited by 7 publications

References 75 publications

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

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

Alcohol and breast cancer

Biochemical Mechanisms Associating Alcohol Use Disorders with Cancers

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