Somiranjan Ghosh1, Partha S Mitra2, Christopher A Loffredo3, Tomas Trnovec4, Lubica Murinova4, Eva Sovcikova4, Svetlana Ghimbovschi5, Shizhu Zang2, Eric P Hoffman5, Sisir K Dutta6. 1. Molecular Genetics Laboratory, Department of Biology, Howard University, Washington, DC 20059, USA. Electronic address: sghosh@howard.edu. 2. Molecular Genetics Laboratory, Department of Biology, Howard University, Washington, DC 20059, USA. 3. Department of Oncology & Department of Biostatistics, Georgetown University, Washington, DC 20057, USA. 4. Department of Environmental Medicine, Slovak Medical University, Bratislava, Slovak Republic. 5. Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA. 6. Molecular Genetics Laboratory, Department of Biology, Howard University, Washington, DC 20059, USA. Electronic address: sdutta@howard.edu.
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.
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.
Authors: Somiranjan Ghosh; Supriyo De; Yongqing Chen; Darryl C Sutton; Folahan O Ayorinde; Sisir K Dutta Journal: Environ Int Date: 2010-08-17 Impact factor: 9.621
Authors: Partha Sarathi Mitra; Somiranjan Ghosh; Shizhu Zang; Dean Sonneborn; Irva Hertz-Picciotto; Tomas Trnovec; Lubica Palkovicova; Eva Sovcikova; Svetlana Ghimbovschi; Eric P Hoffman; Sisir K Dutta Journal: Environ Int Date: 2011-12-08 Impact factor: 9.621
Authors: Kazuko Masuo; Nora E Straznicky; Gavin W Lambert; Tomohiro Katsuya; Ken Sugimoto; Hiromi Rakugi; Florentia Socratous; Jacqueline Hastings; Elisabeth A Lambert; Toshio Ogihara; Murray D Esler Journal: Hypertens Res Date: 2008-06 Impact factor: 3.872
Authors: Mai A Elobeid; Miguel A Padilla; David W Brock; Douglas M Ruden; David B Allison Journal: Int J Environ Res Public Health Date: 2010-07-23 Impact factor: 3.390
Authors: Somiranjan Ghosh; Christopher A Loffredo; Partha S Mitra; Tomas Trnovec; Lubica Palkovicova Murinova; Eva Sovcikova; Eric P Hoffman; Kepher H Makambi; Sisir K Dutta Journal: Environ Sci Pollut Res Int Date: 2017-11-15 Impact factor: 4.223
Authors: Zarish Noreen; Christopher A Loffredo; Attya Bhatti; Jyothirmai J Simhadri; Gail Nunlee-Bland; Thomas Nnanabu; Peter John; Jahangir S Khan; Somiranjan Ghosh Journal: Int J Environ Res Public Health Date: 2020-08-13 Impact factor: 3.390
Authors: Peter Sseruwagi; James Wainaina; Joseph Ndunguru; Robooni Tumuhimbise; Fred Tairo; Jian-Yang Guo; Alice Vrielink; Amanda Blythe; Tonny Kinene; Bruno De Marchi; Monica A Kehoe; Sandra Tanz; Laura M Boykin Journal: Gates Open Res Date: 2018-03-08