title: 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 microM), or Zn (50 microM) 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 > or = 2.0 or < 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.
authors.affiliation: Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Li
authors.forename: Jackie
authors.initials: J
authors.lastname: Stonehuerner
authors.forename: Robert B
authors.initials: RB
authors.lastname: Devlin
authors.forename: Yuh-Chin T
authors.initials: YC
authors.lastname: Huang
mesh_terms: D001980:Bronchi / Q000166:cytology*; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic / Q000235:genetics; D014639:Vanadium / Q000633:toxicity*; D015032:Zinc / Q000633:toxicity*
chemical_list: D014639:Vanadium; D015032:Zinc