You are here:
Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array
Citation:
Mo, J., Y. Xia, Z. Ning, L. He, M. Davidson, D. M. DEMARINI, T. J. WADE, AND J. S. MUMFORD. Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array . International Journal of Environmental Research and Public Health. Molecular Diversity Preservation International, Basel, Switzerland, doi:10.3390:2090-2108, (2011).
Impact/Purpose:
assessment by real time PCR array
Description:
Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We selected the 48 genes on the array based on previous cDNA microarray studies and proposed modes of action of arsenic. Linear regression analysis was used to identify the differentially expressed genes associated with arsenic exposure in the subjects based on arsenic levels in the individual wells of each subject, and also individual urinary and toe nail levels of arsenic. In the human subjects, we found that expression of tumor necrosis factor-a (TNF-a), which activates both inflammation and NF-lCB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-uM arsenic. Alteration of some common pathways, including those involved in oxidative stress and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes. TLDA is a useful tool for identifying and confirming such biomarkers in vivo and in vitro in specific cell types, such as cardiomyocytes. Acknowledgements We thank the staff members of the Inner Mongolia Center for Endemic Disease Control and Research and Ba Men Anti-epidemic Station who participated in this study. The research described here has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
