Induction of buccal mucosal apoptosis with chronic alcohol ingestion

Slomiany, Bronislaw L.; Piotrowski, J.; Piotrowski, E.; Slomiany, Amalia

doi:10.1080/15216549800201392

Cited by 15 publications

(18 citation statements)

References 11 publications

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“…As we progress from zygote to death, our stem cells acquire DNA changes that increase our risk of Importantly, ethanol causes cell death at the concentrations present in alcoholic beverages [18][19][20][21].…”

Section: Discussionmentioning

confidence: 99%

A local mechanism by which alcohol consumption causes cancer

López‐Lázaro

2016

Oral Oncology

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Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect has been overlooked probably because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of endogenous and exogenous DNA-damaging agents (e.g., reactive oxygen species, acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Because the cytotoxic activity of ethanol is concentration-dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages. The local cytotoxic effect of ethanol can also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.

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Section: Discussionmentioning

confidence: 99%

A local mechanism by which alcohol consumption causes cancer

López‐Lázaro

2016

Oral Oncology

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“…The animals were maintained for the initial accommodation week on a regular chow diet and then divided into groups with 12 animals in each, and pair-fed for a period of 9 weeks either with ethanol-containing diet (36% of total calories as ethanol) or a diet where the ethanol was replaced isocalorically with maltodextrin (4,5). The animals were fasted for 24h prior to the experimentation, killed, their buccal mucosa dissected, and the individual collections frozen in liquid nitrogen (6).…”

Section: Methodsmentioning

confidence: 99%

“…The animals were fasted for 24h prior to the experimentation, killed, their buccal mucosa dissected, and the individual collections frozen in liquid nitrogen (6). For quantitative measurements of epithelial cells apoptosis, the buccal mucosal scrapings were minced by passage through a 50-mesh grid, the cells were dispersed by homogenization and collected by centrifugation (4,5). The assays were carried out with a sandwich enzyme immunoassay directed against cytoplasmic histone-associated DNA fragments according to the manufacturer's (Boehringer Mannheim) instruction.…”

Section: Methodsmentioning

confidence: 99%

“…The assays were carried out with a sandwich enzyme immunoassay directed against cytoplasmic histone-associated DNA fragments according to the manufacturer's (Boehringer Mannheim) instruction. The cells were lysed in the lysis buffer, centrifuged, and the diluted supernatant containing the cytoplasmic histone-associated DNA fragments reacted in the microtitrator wells with immobilized anti-histone antibody, and the complex processed for spectrophotometric detection (5).…”

Section: Methodsmentioning

confidence: 99%

“…The accumulating data with animal model indicate that chronic ethanol consumption leads to a marked enhancement in buccal epithelial cells apoptosis triggered by an increase in oral mucosal expression of proinflammatory cytokine, TNF-(~, and the repression of the regulatory cytokine, IL-4 (4,5). Equally deleterious consequences of chronic alcohol diet on the soft oral tissue integrity is the increase in buccal mucosal release of a potent vasoactive peptide, ET-1 (6), and disturbances in nitric oxide, an important mediator of mucosal defenses and a key molecule involved in the signaling events associated with apoptotic cell death (6 -10).…”

Section: Introductionmentioning

confidence: 99%

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Activation of apoptotic caspase‐3 and nitric oxide synthase‐2 in buccal mucosa with chronic alcohol ingestion

Slomiany

Piotrowski

et al. 1998

IUBMB Life

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SUMMARYApoptosis, the process of programmed cell death, involves activation of caspase proteases cascade that remains under the regulatory control of nitric oxide. In this study, we investigated the activity of a key apoptotic protease, caspase-3, and the expression of nitric oxide synthase-2 (NOS-2) associated with buccal epithelial cells apoptosis induced by chronic ethanol diet. The assays revealed that a 7.9-fold enhancement in buccal epithelial cells apoptosis, observed in the alcohol diet group, was accompanied by a 37.6-fold increase in caspase-3 activity and a 10.1-fold increase in NOS-2. Furthermore, the expression of NOS-2 showed a positive correlation (r = 0.92) with the extent of changes induced in caspase-3 activity. These results implicate caspase-3 in the process of alcohol-induced epithelial cells apoptosis, and point towards participation of NOS-2 in the amplification of the cell death signaling cascade.

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Ethanol-Induced Apoptosis in Mouse Liver

Zhou¹,

Sun²,

Kang

2001

The American Journal of Pathology

115

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Hepatic apoptosis has been shown to occur in both experimental and clinical alcoholic liver disease, but the signaling pathway remains unknown. This study was undertaken to examine specifically the involvement of the upstream signals, Fas and cytochrome c, in alcohol-induced caspase-3 activation and apoptosis in the liver. Male FVB mice were administrated intragastrically a single dose of alcohol at 6 g/kg, which has been shown to represent binge drinking in humans. Hepatic apoptosis was detected by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Active form of caspase-3 was identified by immunoperoxidase staining and confirmed by immunogold labeling and was found to be in the cytosol and nucleus. Enzymic assay further confirmed caspase-3 activation and nucleus localization. Systemic administration of caspase-3 inhibitor, Ac-DEVD-FMK, inhibited caspase-3 activity and abrogated apoptosis. Elevation of cytosolic cytochrome c was found by immunoperoxidase staining, immunogold labeling, and Western blot. Increased Fas ligand expression was detected by immunoperoxidase staining. Intravenous administration of a neutralizing Fas ligand monoclonal antibody resulted in suppression of caspase-3 activation and attenuation of apoptosis, but did not inhibit mitochondrial cytochrome c release. The results thus demonstrate that Fas/Fas ligand system-mediated caspase-3 activation plays a central role in the ethanol-induced hepatic apoptosis.

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Induction of buccal mucosal apoptosis with chronic alcohol ingestion

Cited by 15 publications

References 11 publications

A local mechanism by which alcohol consumption causes cancer

A local mechanism by which alcohol consumption causes cancer

Activation of apoptotic caspase‐3 and nitric oxide synthase‐2 in buccal mucosa with chronic alcohol ingestion

Ethanol-Induced Apoptosis in Mouse Liver

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