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Genes (Basel). 2017 May 3;8(5). pii: E132. doi: 10.3390/genes8050132.

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

Author information

1
Statistical Genetics, Axio Research LLC, 4th Ave. Suite 200, Seattle, WA 98121, USA. sangsoonw@axioresearch.com.
2
Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. kygaohong@gmail.com.
3
Statistical Genetics, Axio Research LLC, 4th Ave. Suite 200, Seattle, WA 98121, USA. davidh@axioresearch.com.
4
Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. wolfgang.zacharias@louisville.edu.
5
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. wolfgang.zacharias@louisville.edu.
6
RAI Services Company, 401 N. Main Street, Winston-Salem, NC 27101, USA. liug@rjrt.com.
7
RAI Services Company, 401 N. Main Street, Winston-Salem, NC 27101, USA. trann1@rjrt.com.
8
RAI Services Company, 401 N. Main Street, Winston-Salem, NC 27101, USA. prasadg@rjrt.com.

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.

KEYWORDS:

aldo-keto reductases; cigarette smoke; nicotine; oral cavity cells; smokeless tobacco products; xenobiotic metabolism

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