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Cancer Biol Ther. 2018;19(9):773-785. doi: 10.1080/15384047.2018.1470724. Epub 2018 May 29.

Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes.

Author information

1
a Institute of Bioinformatics, International Tech Park , Bangalor , India.
2
b School of Biotechnology , Kalinga Institute of Industrial Technology , Bhubaneswar , India.
3
c School of Biotechnology , Amrita Vishwa Vidyapeetham , Kollam , India.
4
d Medgenome Labs Pvt. Ltd. , Bangalore , India.
5
e NIMHANS-IOB Bioinformatics and Proteomics Laboratory , Neurobiology Research Centre, National Institute of Mental Health and Neurosciences , Bangalore , India.
6
f Center for Systems Biology and Molecular Medicine , Yenepoya , Mangalore , India.
7
g Dept. of Biochemistry & Molecular Biology , School of Life Sciences, Pondicherry University , Pondicherry , India.
8
h Department of Surgery , UC San Diego, Moores Cancer Center , La Jolla , CA , USA.
9
i Department of Otolaryngology-Head and Neck Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.

Abstract

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8 months. We employed whole exome sequencing (WES) and quantitative proteomics to investigate the molecular alterations in oral keratinocytes chronically exposed to smoke/ chewing tobacco. Exome sequencing revealed distinct mutational spectrum and copy number alterations in smoke/ chewing tobacco treated cells. We also observed differences in proteomic alterations. Proteins downstream of MAPK1 and EGFR were dysregulated in smoke and chewing tobacco exposed cells, respectively. This study can serve as a reference for fundamental damages on oral cells as a consequence of exposure to different forms of tobacco.

KEYWORDS:

Orbitrap Fusion; carcinogenesis; chronic exposure; high-throughput; smoking

PMID:
29723088
PMCID:
PMC6154853
[Available on 2019-05-29]
DOI:
10.1080/15384047.2018.1470724

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