| Discrimination of Vanadium from Zinc Using Gene Profiling in Human Bronchial Epithelial Cells Zhuowei Li,1 Jackie Stonehuerner,2 Robert B. Devlin,2 and Yuh-Chin T. Huang2 1Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, North Carolina, USA; 2National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA
Abstract
We hypothesized that gene expression profiling may discriminate vanadium from zinc in human bronchial epithelial cells (HBECs) . RNA from HBECs exposed to vehicle, V (50 µM) , or Zn (50 µM) for 4 hr (n = 4 paired experiments) was hybridized to Affymetrix Hu133A chips. Using one-class t-test with p < 0.01, we identified 140 and 76 genes with treatment:control ratios ≥ 2.0 or ≤ 0.5 for V and Zn, respectively. We then categorized these genes into functional pathways and compared the number of genes in each pathway between V and Zn using Fisher's exact test. Three pathways regulating gene transcription, inflammatory response, and cell proliferation distinguished V from Zn. When genes in these three pathways were matched with the 163 genes flagged by the same statistical filtration for V:Zn ratios, 12 genes were identified. The hierarchical clustering analysis showed that these 12 genes discriminated V from Zn and consisted of two clusters. Cluster 1 genes (ZBTB1, PML, ZNF44, SIX1, BCL6, ZNF450) were down-regulated by V and involved in gene transcription, whereas cluster 2 genes (IL8, IL1A, PTGS2, DTR, TNFAIP3, CXCL3) were up-regulated and linked to inflammatory response and cell proliferation. Also, metallothionein 1 genes (MT1F, MT1G, MT1K) were up-regulated by Zn only. Thus, using microarray analysis, we identified a small set of genes that may be used as biomarkers for discriminating V from Zn. The novel genes and pathways identified by the microarray may help us understand the pathogenesis of health effects caused by environmental V and Zn exposure. Key words: cell proliferation, inflammation, interleukin-1, interleukin-8, metal, microarray, transcription. Environ Health Perspect 113:1747-1754 (2005) . doi:10.1289/ehp.7947 available via http://dx.doi.org/ [Online 21 June 2005]
Address correspondence to Y.-C.T. Huang, Human Study Facilities, U.S. EPA, CB 7315, 104 Mason Farm Rd., Chapel Hill, NC 27599 USA. Telephone: (919) 843-9504. Fax: (919) 966-6271. E-mail: huang.tony@epa.gov We thank A. Ghio and L. Dailey of the Human Studies Division of the U.S. Environmental Protection Agency (U.S. EPA) for performing bronchoscopic brushings and cell culture, respectively. The research described in this article has been reviewed by the U.S. EPA Health Effects and Environmental Research Laboratory and has been approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the U.S. EPA, nor does mention of the trade names or commercial products constitute endorsement or recommendation for use. The authors declare they have no competing financial interests. Received 19 January 2005 ; accepted 21 June 2005.
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