Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: Identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility

Abstract

Drinking arsenic-contaminated water is associated with increased risk of neoplasias of the skin, lung, bladder and possibly other sites, as well as other diseases. Earlier, we showed that human lymphoblast lines from different normal unexposed donors showed variable sensitivities to the toxic effects of arsenite. In the present study, we used microarray analysis to compare the basal gene expression profiles between two arsenite-resistant (GM02707, GM00893) and two arsenite-sensitive lymphoblast lines (GM00546, GMO00607). A number of genes were differentially expressed in arsenite-sensitive and arsenite-resistant cells. Among these, γ-glutamyltranspeptidase 1 (GGT1) and NFB inhibitor-epsilon (NFKBIE) showed higher expression levels in arsenite-resistant cells. RT-PCR analysis with gene-specific primers confirmed these results. Reduction of GGT1 expression level in arsenite resistant lymphoblasts with GGT1-specific siRNA resulted in increased cell sensitivity to arsenite. In conclusion, we have demonstrated for the first time that expression levels of GGT1 and possibly NFKBIE might be useful as biomarkers of genetic susceptibility to arsenite. Expression microarrays can thus be exploited for identifying additional biomarkers of susceptibility to arsenite and to other toxicants.

High-concentration Epigallocatechin Gallate Treatment Causes Endoplasmic Reticulum Stress-mediated Cell Death in HepG2 Cells

“…In this study, NFKBIE was differentially expressed at 6 h (2.6-fold) and 12 h (2.2-fold), but at 24 h it was not significantly expressed (1.1-fold). NFKBIE is known as a member of the family of NF-κB inhibitory proteins (IκBs) that interact with NF-κB in unstimulated cells (Komissarova et al, 2008),…”

Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays

“…The transcription factor Nrf2 is a central regulator in the activation of many genes related to antioxidant response, such as glutathione S-transferase ( GST ), NAD(P)H , quinine reductases ( NQO1 ), heat shock protein, and heme oxygenase 1 ( HO-1 ). Although we did not have GGT1 or NFKBIE on our array, their expression levels in lymphoblasts may be biomarkers of susceptibility arsenic toxicity [ 38 ].…”