Discrimination of Vanadium from Zinc Using Gene Profiling in Human Bronchial Epithelial Cells

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.

Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation

“…Some vanadium salts (e.g. VOSO 4 ) in vitro also can up-regulate genes associated with proliferation, including: AP-1, Ras, C-Raf-1, MAPK, p53 and NF-B (Pandey et al 1999;Ye et al 1999;Mukherjee et al 2004;Li et al 2005). Due to the chemical/structural similarity between vanadate and phosphate ions, V is also able to stimulate cell cycle pathways by activating mitogens and kinases such as Syk family, ERK1/2, MAPK and PI3K (Krejsa et al 1997;Morinville et al 1998;Wang & Bonner 2000).…”

Genomic analysis of human lung fibroblasts exposed to vanadium pentoxide to identify candidate genes for occupational bronchitis

“…Li and colleagues used microarray analysis to investigate gene expression changes in human bronchial epithelial cells exposed to vanadium or zinc and identifed a small set of genes that could be used as biomarkers for discriminating vanadium from zinc [42]. They also reported that IL8 and PTGS2 (COX-2) were induced several-fold by vanadium but not by zinc.…”

Up-regulation of Tissue Factor in Human Pulmonary Artery Endothelial Cells after Ultrafine Particle Exposure

“…RNA target preparation and hybridization to the Affymetrix HG U133 plus 2.0 GeneChip oligonucleotide microarray (Affymetrix, Inc., Santa Clara, CA) was performed by Expression Analysis, Inc. as described previously (Li et al 2005b). Fluorescent images were detected in a GeneChip Scanner 3000 and expression data was extracted using the default settings in the Microarray Suite 5.0 software (Affymetrix).…”