Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males.

BMC Medical Genomics
Peter C CharlesGeorge A Stouffer

Abstract

Strong epidemiologic evidence correlates tobacco use with a variety of serious adverse health effects, but the biological mechanisms that produce these effects remain elusive. We analyzed gene transcription data to identify expression spectra related to tobacco use in circulating leukocytes of 67 Caucasian male subjects. Levels of cotinine, a nicotine metabolite, were used as a surrogate marker for tobacco exposure. Significance Analysis of Microarray and Gene Set Analysis identified 109 genes in 16 gene sets whose transcription levels were differentially regulated by nicotine exposure. We subsequently analyzed this gene set by hyperclustering, a technique that allows the data to be clustered by both expression ratio and gene annotation (e.g. Gene Ontologies). Our results demonstrate that tobacco use affects transcription of groups of genes that are involved in proliferation and apoptosis in circulating leukocytes. These transcriptional effects include a repertoire of transcriptional changes likely to increase the incidence of neoplasia through an altered expression of genes associated with transcription and signaling, interferon responses and repression of apoptotic pathways.

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Citations

Sep 12, 2015·Chemical Research in Toxicology·Danyel G J JennenJos C S Kleinjans
Sep 1, 2015·Atherosclerosis·Henri WeidmannEwa Ninio
Dec 3, 2014·Toxicology Letters·Hyun-Kyung NaMihi Yang
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Jul 12, 2011·Cancer Prevention Research·Melissa RotunnoMaria Teresa Landi
Nov 21, 2017·The American Journal of Pathology·Saranya RaviJonathan C Schisler

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Methods Mentioned

BETA
blood draw
electrophoresis
ELISA
Polymerase Chain Reaction
PCR
GTPase

Software Mentioned

R Statistical Language and Environment ( R
Gene Set Analysis ( GSA
JavaTreeView
GSA
Perl
SAM
Probe Finder
Cluster
GATHER
Gene Set Enrichment Analysis

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