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Transcriptome changes induced in vitro by alcohol‐containing mouthwashes in normal and dysplastic oral keratinocytes
Author(s) -
Fox Simon A.,
Currie Sean S.,
Dalley Andrew J.,
Farah Camile S.
Publication year - 2018
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12704
Subject(s) - transcriptome , genotoxicity , alcohol , comet assay , kegg , carcinogen , gene expression , biology , in vitro , dna damage , microbiology and biotechnology , gene , medicine , biochemistry , dna , toxicity
Background The role of alcohol‐containing mouthwash as a risk factor for the development of oral cancer is a subject of conflicting epidemiological evidence in the literature despite alcohol being a recognised carcinogen. The aim of this study was to use in vitro models to investigate mechanistic and global gene expression effects of exposure to alcohol‐containing mouthwash. Methods Two brands of alcohol‐containing mouthwash and their alcohol‐free counterparts were used to treat two oral cell lines derived from normal ( OKF 6‐ TERT ) and dysplastic ( DOK ) tissues. Genotoxicity was determined by Comet assay. RNA ‐seq was performed using the Ion Torrent platform. Bioinformatics analysis used R/Bioconductor packages with differential expression using DE seq2. Pathway enrichment analysis used EnrichR with the WikiPathways and Kegg databases. Results Both cell lines displayed dose‐dependent DNA damage in response to acute exposure to ethanol and alcohol‐containing mouthwashes as well as alcohol‐free mouthwashes reconstituted with ethanol as shown by Comet assay. The transcriptomic effects of alcohol‐containing mouthwash exposure were more complex with significant differential gene expression ranging from >2000 genes in dysplastic ( DOK ) cells to <100 genes in normal ( OKF 6‐ TERT ) cells. Pathway enrichment analysis in DOK cells revealed alcohol‐containing mouthwashes showed common features between the two brands used including DNA damage response as well as cancer‐associated pathways. In OKF 6‐ TERT cells, the most significantly enriched pathways involved inflammatory signalling. Conclusions Alcohol‐containing mouthwashes are genotoxic in vitro to normal and dysplastic oral keratinocytes and induce widespread changes in gene expression. Dysplastic cells are more susceptible to the transcriptomic effects of mouthwash.