Abstract
The risk of cancer due to PCB exposure in humans is highly debated. In eastern Slovakia, high exposure of the population to organochlorines (especially PCBs) was associated with various disease and disorder pathways, viz., endocrine disruption, metabolic disorder & diabetes, and cancer, thereby disturbing several cellular processes, including protein synthesis, stress response, and apoptosis. We have evaluated a Slovak cohort (45-month children, at lower and higher levels of PCB exposure from the environment) for disease and disorder development to develop early disease cancer biomarkers that could shed new light on possible mechanisms for the genesis of cancers under such chemical exposures, and identify potential avenues for prevention.
Microarray studies of global gene expression were conducted from the 45-month-old children on the Affymetrix platform followed by Ingenuity Pathway Analysis (IPA®) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR TaqMan low-density array (TLDA) was performed to further validate the selected genes on the whole blood cells of the most highly exposed children from the study cohort (n = 71).
TP53, MYC, BCL2, and LRP12 differential gene expressions suggested strong relationships between potential future tumor promotion and PCB exposure in Slovak children. The IPA analysis further detected the most important signaling pathways, including molecular mechanism of cancers, prostate cancer signaling, ovarian cancer signaling, P53 signaling, oncostatin M signaling, and their respective functions (viz., prostate cancer, breast cancer, progression of tumor, growth of tumor, and non-Hodgkin’s disease). The results suggest that PCB exposures, even at the early age of these children, may have lifelong consequences for the future development of chronic diseases.
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Acknowledgments
This work received support from U.S. National Institutes of Health grants # R01-CA96525. Thanks to Prof. Gray Harris, Dean of the Graduate School, Howard University for continuing supplemental support to this research initiative. Thanks are also due to the Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS) and Dr. Annapurni Jayam Trouth, MD of Howard University for their assistance with the blood collection from healthy donors, as per approved HU IRB # IRB-07- GSAS-30. The contents of this report are solely the responsibility of the authors.
Glossary
U.S. EPA, United States Environmental Protection Agency
GEO, Gene Expression Omnibus (database)
HEPG2, liver hepatocellular carcinoma cell line (human)
IPA®, Ingenuity Pathway Analysis
MIAME, Minimum Information About a Microarray Experiment
NHL, non-Hodgkin lymphoma
OCs, organochlorine compounds
PCBs, polychlorinated biphenyls
POPs, persistent organic pollutants
qRT-PCR, quantitative real-time polymerases chain reaction
TLDA, TaqMan low-density array
Funding
This study is supported by the 1UO1ES016127-01 from the National Institute of Environmental Health Sciences (NIEHS/NIH), the European Commission through the 7FP project OBELIX (No. 227391), Ministry of Health, Slovak Republic through projects 2007/07-SZU-03, 2012/41-SZU-05, and 2012/47-SZU-11, Slovak Research and Development Agency through projects APVV-0571-12 and APVV-0444-11, the project “Center of Excellence of Environmental Health,” ITMS No. 26240120033, based on the supporting Operational Research and Development Program financed from the European Regional Development Fund, 5G12MD007597-25 (NIMHD, PI: Southerland), and from the R200174 grant from Howard University.
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Responsible editor: Philippe Garrigues
Presented as part at the 9th International PCB Workshop in Kobe, Japan, 9–16 October, 2016 as Poster.
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Ghosh, S., Loffredo, C.A., Mitra, P.S. et al. PCB exposure and potential future cancer incidence in Slovak children: an assessment from molecular finger printing by Ingenuity Pathway Analysis (IPA®) derived from experimental and epidemiological investigations. Environ Sci Pollut Res 25, 16493–16507 (2018). https://doi.org/10.1007/s11356-017-0149-1
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DOI: https://doi.org/10.1007/s11356-017-0149-1