Discovery of Novel Biomarkers by Microarray Analysis of Peripheral Blood Mononuclear Cell Gene Expression in Benzene-Exposed Workers

Abstract

Benzene is an industrial chemical and component of gasoline that is an established cause of leukemia. To better understand the risk benzene poses, we examined the effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression in a population of shoe-factory workers with well-characterized occupational exposures using microarrays and real-time polymerase chain reaction (PCR). PBMC RNA was stabilized in the field and analyzed using a comprehensive human array, the U133A/B Affymetrix GeneChip set. A matched analysis of six exposed–control pairs was performed. A combination of robust multiarray analysis and ordering of genes using paired t-statistics, along with bootstrapping to control for a 5% familywise error rate, was used to identify differentially expressed genes in a global analysis. This resulted in a set of 29 known genes being identified that were highly likely to be differentially expressed. We also repeated these analyses on a smaller subset of 508 cytokine probe sets and found that the expression of 19 known cytokine genes was significantly different between the exposed and the control subjects. Six genes were selected for confirmation by real-time PCR, and of these, CXCL16, ZNF331, JUN, and PF4 were the most significantly affected by benzene exposure, a finding that was confirmed in a larger data set from 28 subjects. The altered expression was not caused by changes in the makeup of the PBMC fraction. Thus, microarray analysis along with real-time PCR confirmation reveals that altered expressions of CXCL16, ZNF331, JUN, and PF4 are potential biomarkers of benzene exposure.

Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics

“…More importantly, linear regression revealed that the relationship between PF4 and CTAP-III was not markedly different when corrected for absolute platelet counts or any of the other measured white blood cell types. These results are an indication that the difference in serum levels of platelet-derived cytokines is not a simple reflection of the decrease in the absolute count of peripheral platelets or other blood cells, further corroborated by our recent observation that expression of PF4 RNA in peripheral blood mononuclear cells was consistently down-regulated in exposed individuals (mean decrease 58%) when compared with unexposed individuals (20).…”

Polymorphisms in Cytokine and Cellular Adhesion Molecule Genes and Susceptibility to Hematotoxicity among Workers Exposed to Benzene

“…Further, a recent report from our study population showed a highly significant increase in IL-4R mRNA expression in peripheral mononuclear cells from benzene-exposed workers (31). The influence of benzene on the production and function of IL-10, IL-12, or VCAM1, and how benzene might alter stem, progenitor, or stromal cell responses to these compounds, is not known.…”

Gene Expression Biomarkers Provide Sensitive Indicators of in Planta Nitrogen Status in Maize

“…Gene expression biomarkers have also been explored in other areas, such as indicators of toxin exposure (Forrest et al, 2005) and longevity therapeutics (Spindler, 2006). In plants, DNA markers are routinely used in breeding applications to follow association and for the introgression of favorable gene alleles that impart desired agronomic traits (for review, see Collard and Mackill, 2008).…”