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Genes 2017, 8(5), 132; doi:10.3390/genes8050132

AKR1C1 as a Biomarker for Differentiating the Biological Effects of Combustible from Non-Combustible Tobacco Products

1
Statistical Genetics, Axio Research LLC, 4th Ave. Suite 200, Seattle, WA 98121, USA
2
Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
3
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
4
RAI Services Company, 401 N. Main Street, Winston-Salem, NC 27101, USA
Co-first authors.
*
Author to whom correspondence should be addressed.
Academic Editor: Selvarangan Ponnazhagan
Received: 24 January 2017 / Revised: 31 March 2017 / Accepted: 25 April 2017 / Published: 3 May 2017
(This article belongs to the Section Human Genomics and Genetic Diseases)
View Full-Text   |   Download PDF [826 KB, uploaded 3 May 2017]   |  

Abstract

Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible ones using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than eight-fold by combustible TPPs. Quantitative real time polymerase chain reaction (qRT-PCR) results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products. View Full-Text
Keywords: aldo-keto reductases; cigarette smoke; smokeless tobacco products; nicotine; oral cavity cells; xenobiotic metabolism aldo-keto reductases; cigarette smoke; smokeless tobacco products; nicotine; oral cavity cells; xenobiotic metabolism
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MDPI and ACS Style

Woo, S.; Gao, H.; Henderson, D.; Zacharias, W.; Liu, G.; Tran, Q.T.; Prasad, G. AKR1C1 as a Biomarker for Differentiating the Biological Effects of Combustible from Non-Combustible Tobacco Products. Genes 2017, 8, 132.

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