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Transcriptional profiling and biological pathway analysis of human equivalence PCB exposure in vitro: indicator of disease and disorder development in humans.
Ghosh, Somiranjan; Mitra, Partha S; Loffredo, Christopher A; Trnovec, Tomas; Murinova, Lubica; Sovcikova, Eva; Ghimbovschi, Svetlana; Zang, Shizhu; Hoffman, Eric P; Dutta, Sisir K.
Afiliação
  • Ghosh S; Molecular Genetics Laboratory, Department of Biology, Howard University, Washington, DC 20059, USA. Electronic address: sghosh@howard.edu.
  • Mitra PS; Molecular Genetics Laboratory, Department of Biology, Howard University, Washington, DC 20059, USA.
  • Loffredo CA; Department of Oncology & Department of Biostatistics, Georgetown University, Washington, DC 20057, USA.
  • Trnovec T; Department of Environmental Medicine, Slovak Medical University, Bratislava, Slovak Republic.
  • Murinova L; Department of Environmental Medicine, Slovak Medical University, Bratislava, Slovak Republic.
  • Sovcikova E; Department of Environmental Medicine, Slovak Medical University, Bratislava, Slovak Republic.
  • Ghimbovschi S; Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA.
  • Zang S; Molecular Genetics Laboratory, Department of Biology, Howard University, Washington, DC 20059, USA.
  • Hoffman EP; Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA.
  • Dutta SK; Molecular Genetics Laboratory, Department of Biology, Howard University, Washington, DC 20059, USA. Electronic address: sdutta@howard.edu.
Environ Res ; 138: 202-16, 2015 Apr.
Article em En | MEDLINE | ID: mdl-25725301
ABSTRACT
BACKGROUND AND

AIMS:

Our earlier gene-expression studies with a Slovak PCBs-exposed population have revealed possible disease and disorder development in accordance with epidemiological studies. The present investigation aimed to develop an in vitro model system that can provide an indication of disrupted biological pathways associated with developing future diseases, well in advance of the clinical manifestations that may take years to appear in the actual human exposure scenario.

METHODS:

We used human Primary Blood Mononuclear Cells (PBMC) and exposed them to a mixture of human equivalence levels of PCBs (PCB-118, -138, -153, -170, -180) as found in the PCBs-exposed Slovak population. The microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR Taqman Low Density Array (TLDA) was done to further validate the selected 6 differentially expressed genes of our interest, viz., ARNT, CYP2D6, LEPR, LRP12, RRAD, TP53, with a small population validation sample (n=71).

RESULTS:

Overall, we revealed a discreet gene expression profile in the experimental model that resembled the diseases and disorders observed in PCBs-exposed population studies. The disease pathways included endocrine system disorders, genetic disorders, metabolic diseases, developmental disorders, and cancers, strongly consistent with the evidence from epidemiological studies.

INTERPRETATION:

These gene finger prints could lead to the identification of populations and subgroups at high risk for disease, and can pose as early disease biomarkers well ahead of time, before the actual disease becomes visible.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Bifenilos Policlorados / Exposição Ambiental / Poluentes Ambientais Limite: Adolescent / Adult / Child / Female / Humans / Male País/Região como assunto: America do norte / Europa Idioma: En Revista: Environ Res Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Bifenilos Policlorados / Exposição Ambiental / Poluentes Ambientais Limite: Adolescent / Adult / Child / Female / Humans / Male País/Região como assunto: America do norte / Europa Idioma: En Revista: Environ Res Ano de publicação: 2015 Tipo de documento: Article