Preprint Article Version 1 This version is not peer-reviewed

Alcohol-containing Mouthwashes and Oral Cancer: A Mechanistic Explanation

Version 1 : Received: 6 March 2018 / Approved: 6 March 2018 / Online: 6 March 2018 (14:28:22 CET)

How to cite: Calderón-Montaño, J.M.; Jiménez-Alonso, J.J.; Guillén-Mancina, E.; Burgos-Morón, E.; Lopez-Lazaro, M. Alcohol-containing Mouthwashes and Oral Cancer: A Mechanistic Explanation. Preprints 2018, 2018030044 (doi: 10.20944/preprints201803.0044.v1). Calderón-Montaño, J.M.; Jiménez-Alonso, J.J.; Guillén-Mancina, E.; Burgos-Morón, E.; Lopez-Lazaro, M. Alcohol-containing Mouthwashes and Oral Cancer: A Mechanistic Explanation. Preprints 2018, 2018030044 (doi: 10.20944/preprints201803.0044.v1).

Abstract

Objective: To provide mechanistic evidence for the epidemiological link between long-term use of alcohol containing mouthwashes and oral cancer.Methods: Human epithelial keratinocytes were exposed for 30 seconds to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay.Results: A marked cytotoxic effect was observed for ethanol concentrations of 20% and above. Conclusions: The cytotoxicity of ethanol can explain the epidemiological association between mouthwash use and oral cancer. Recent findings indicate that the risk of developing cancer in a tissue is strongly determined by the number of stem cell divisions accumulated by the tissue during a person's lifetime; cell division is a major source of mutations and other cancer-promoting errors. Since cell death activates the division of stem cells, the cytotoxicity of ethanol on the cells lining the oral mucosa will promote the division of the stem cells located in deeper layers to produce new cells to regenerate the damaged epithelium. If we regularly use mouthwashes containing cytotoxic concentrations of ethanol, we will force the stem cells of the oral cavity to divide more often than usual and our risk of developing oral cancer will probably increase.Clinical significance: Many mouthwashes contain percentages of ethanol above 20%. Because ethanol is not crucial to prevent and reduce gingivitis and plaque, members of the dental team should consider the potential risk of oral cancer associated with frequent use of alcohol containing mouthwashes when advising their patients.

Subject Areas

cancer prevention; carcinogenesis; oral cancer; pharynx cancer; mouthrinses; ethanol.

Readers' Comments and Ratings (2)

Comment 1
Received: 8 March 2018
Commenter: Marit Zinöcker
The commenter has declared there is no conflict of interests.
Comment: Very interesting topic.
Have you considered the contribution of emulsifying agents in these mouthwashes?
Severeal of them contain for instance P-80, an emulsifier that has been demostrated to increase the pro-inflammatory potential of the gut micribiota. It cold possibly affect the oral microbiota as well.
https://www.ncbi.nlm.nih.gov/pubmed/27430014 https://www.ncbi.nlm.nih.gov/pubmed/28325746
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Comment 2
Received: 14 March 2018
Commenter: Miguel Lopez-Lazaro
The commenter has declared there is no conflict of interests.
Comment: Thank you for your comment. I think it is possible. The division of stem cells is actually controlled by multiple local and systemic factors including changes in the microbiota (10.1016/j.critrevonc.2018.01.010), and we do not exclude the possibility that other mothwash components (e.g., P-80) can play a role in the potential carcinogenicity of mouthwashes. However, we think that the accumulation of cell divisions in stem cells promoted by the continuous exposure to cytotoxic concentrations of ethanol is the main mechanism by which alcohol-containing mouthwashes can increase the risk of oral cancer. If one continuously damages the cells lining the oral cavity, the stem cells responsible for their renewal will divive more often than usual to maintain the tissue in homeostasis; otherwise, tissue functionality would be compromised. Since cell division is a major source of mutations and other DNA alterations, these extra number of cell divisions accumulated by the stem cells will lead to an extra number of DNA alterations that will increase their risk of malignant transformation. The striking association recently found between the number of stem cell divisions accumulated by a tissue during a person's lifetime and the risk of cancer in the tissue strongly supports this mechanism of carcinogenesis.
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