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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.
相似文献In Brazil, specifically in the Doce River basin, there is still a great lack of studies on temporal and spatial trends in water quality, since the water quality in the monitoring campaigns is basically evaluated when it comes down to the concentrations of monitored variables. In this sense, the objective of this work was to perform a temporal and spatial trend analysis of water quality data in the Minas Gerais portion of the Doce River basin, Brazil. For this, the Mann–Kendall, seasonal Mann–Kendall and Spearman correlation tests were used in the temporal analysis and the cluster analysis in the spatial analysis. In the analysis of temporal trends, the analyses were performed using the values of the National Sanitation Foundation Water Quality Index (NSFWQI) and the variables that compose it. In the analysis of spatial trends, the stations were evaluated only based on the WQI. With the results of the analysis of temporal trend, it was identified that most stations did not present a statistically significant trend for the WQI. In the stations that presented trends of quality reduction, most of them are in densely populated areas, demonstrating the strong influence of the poor sanitary conditions of the municipalities to the water quality of the basin. When analyzing the variables that compose the WQI, the results found for nitrate demonstrated that water quality deterioration is also affected by the diffuse pollution originating from farming areas. The results for Escherichia coli reinforced the impact of the discharge of domestic effluents and demonstrated the absence of a significative trend is still of concern because it can represent the maintenance of a degradation state in the water bodies. In the spatial trend analysis, the CA grouped the monitoring stations into six clusters based on their similarity among the WQI values, and, together with the results of the other analyses, it was verified that the Caratinga River basin (UGRH5 Caratinga) presented the highest degree of pollution. It was also possible to identify five stations that can be reallocated or deactivated since they have similarities with other stations located in the same watercourse.
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