Perturbation of defense pathways by low-dose arsenic exposure in zebrafish embryos.
BACKGROUND: Exposure to arsenic is a critical risk factor in the complex interplay among genetics, the environment, and human disease. Despite the potential for in utero exposure, the mechanism of arsenic action on vertebrate development and disease is unknown. OBJECTIVES: The objective of this stud...
| Publicado en: | Environmental Health Perspectives Vol. 117; no. 6; pp. 981 - 988 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
National Institute of Environmental Health Sciences
Jun2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105395308&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105395308 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Jun2009 vid: 117 iid: 6 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 105395308 2010358447 10.1289/ehp.0900555 NLM19590694 105395308 ppf: 981 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Perturbation of defense pathways by low-dose arsenic exposure in zebrafish embryos. aug: au: Mattingly CJ Hampton TH Brothers KM Griffin NE Planchart A affil: Mount Desert Island Biological Laboratory, Salisbury Cove, Maine 04679, USA. sug: subj: Arsenic Adverse Effects Embryo Drug Effects Gene Expression Drug Effects Vertebrates Animal Studies Biochips Fish Funding Source Polymerase Chain Reaction RNA T-Tests ab: BACKGROUND: Exposure to arsenic is a critical risk factor in the complex interplay among genetics, the environment, and human disease. Despite the potential for in utero exposure, the mechanism of arsenic action on vertebrate development and disease is unknown. OBJECTIVES: The objective of this study was to identify genes and gene networks perturbed by arsenic during development in order to enhance understanding of the molecular mechanisms of arsenic action. METHODS: We exposed zebrafish embryos at 0.25-1.25 hr postfertilization to 10 or 100 ppb arsenic for 24 or 48 hr. We then used total RNA to interrogate genome microarrays and to test levels of gene expression changes by quantitative real-time polymerase chain reaction (QPCR). Computational analysis was used to identify gene expression networks perturbed by arsenic during vertebrate development. RESULTS: We identified a set of 99 genes that responded to low levels of arsenic. Nineteen of these genes were predicted to function in a common regulatory network that was significantly associated with immune response and cancer (p < 10(-41)). Arsenic-mediated expression changes were validated by QPCR. CONCLUSIONS: In this study we demonstrated that arsenic significantly down-regulates expression levels of multiple genes potentially critical for regulating the establishment of an immune response. The data also provide molecular evidence consistent with phenotypic observations reported in other model systems. Additional mechanistic studies will help explain molecular events regulating early stages of the immune system and long-term consequences of arsenic-mediated perturbation of this system during development. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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