Systems biology of human benzene exposure

Abstract

Toxicogenomic studies, including genome-wide analyses of susceptibility genes (genomics), gene expression (transcriptomics), protein expression (proteomics), and epigenetic modifications (epigenomics), of human populations exposed to benzene are crucial to understanding gene-environment interactions, providing the ability to develop biomarkers of exposure, early effect and susceptibility. Comprehensive analysis of these toxicogenomic and epigenomic profiles by bioinformatics in the context of phenotypic endpoints, comprises systems biology, which has the potential to comprehensively define the mechanisms by which benzene causes leukemia. We have applied this approach to a molecular epidemiology study of workers exposed to benzene. Hematotoxicity, a significant decrease in almost all blood cell counts, was identified as a phenotypic effect of benzene that occurred even below 1ppm benzene exposure. We found a significant decrease in the formation of progenitor colonies arising from bone marrow stem cells with increasing benzene exposure, showing that progenitor cells are more sensitive to the effects of benzene than mature blood cells, likely leading to the observed hematotoxicity. Analysis of transcriptomics by microarray in the peripheral blood mononuclear cells of exposed workers, identified genes and pathways (apoptosis, immune response, and inflammatory response) altered at high (>10ppm) and low (<1ppm) benzene levels. Serum proteomics by SELDI-TOF-MS revealed proteins consistently down-regulated in exposed workers. Preliminary epigenomics data showed effects of benzene on the DNA methylation of specific genes. Genomic screens for candidate genes involved in susceptibility to benzene toxicity are being undertaken in yeast, with subsequent confirmation by RNAi in human cells, to expand upon the findings from candidate gene analyses. Data on these and future biomarkers will be used to populate a large toxicogenomics database, to which we will apply bioinformatic approaches to understand the interactions among benzene toxicity, susceptibility genes, mRNA, and DNA methylation through a systems biology approach.

Electronic noses for monitoring benzene occupational exposure in biological samples of Egyptian workers

“…Under conditions prevailing at the workplace, benzene is absorbed by inhalation, although dermal absorption of liquid benzene is also significant [2]. Benzene metabolism has been extensively studied in various animal models, in vitro incubations, and by theoretical calculations [2][3][4][5][6][7], with evidences that it is impossible to distinguish between occupational and environmental exposure when the benzene level in the workplace is less than 100 μg/m 3 [19].…”

“…Moreover, chronic exposure to benzene can cause fatigue, nervousness, irritability, blurred vision, and labored breathing. Repeated skin contact can cause redness, blistering, and scaly dermatitis [2,4,5]. Recent studies showed significant hematological disorders, chromosomal aberrations as well as relatively high concentration of phenol in 24-hour urine samples due to exposure to benzene in chemical industry workers [4][5][6][7].…”

“…Repeated skin contact can cause redness, blistering, and scaly dermatitis [2,4,5]. Recent studies showed significant hematological disorders, chromosomal aberrations as well as relatively high concentration of phenol in 24-hour urine samples due to exposure to benzene in chemical industry workers [4][5][6][7]. Furthermore, blood disorders may lead to anemia and other diseases causing a significant reduction in working capacity and activity of workers, loss of working hours, and the increase in the costs of medical care of the affected workers [4].…”

Toxicogenomics and Cancer Susceptibility: Advances with Next-Generation Sequencing

“…Air pollution Globally Decreased [199] Affected [207] Affected [211] Other Chemicals Benzene Affected [200] Increased Phosphorylation [208] Affected [216] Bisphenol A Globally Decreased [201] Increased Trimethylation [209] Affected [217] Ning et al Page 34 Table 3 Summary of Next-Generation Sequencing Platforms …”

Omics in population studies: A molecular epidemiology perspective

“…Certainly, there have been success stories, for example: the human papillomavirus-cervical cancer association [Schiffman et al, 2007], the underpinning of the mechanism of action of certain chemical carcinogens (e.g., benzene, formaldehyde) [Zhang et al, 2010;IARC Monographs, 1995;Lan et al, 2004], the reduction in exposure misclassification (e.g., aflatoxin exposure and hepatocellular carcinoma) [Ross et al, 1992], and the identification of susceptibility factors through functional assays (e.g., chromosomal aberration, micronucleus assay) [Hagmar et al, 1998;Bonassi et al, 2007]. However, even with these advances many of the environmental factors that modify disease susceptibility remain elusive.…”