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Final Progress Reports: University of California-Berkeley: Biomarkers of Benzene Exposure and Leukemia Risk

Superfund Research Program

Biomarkers of Benzene Exposure and Leukemia Risk

Project Leader: Martyn T. Smith
Co-Investigator: Stephen M. Rappaport
Grant Number: P42ES004705
Funding Period: 2011-2017
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Final Progress Reports

Year:   2016 

The overall goal of this project is to use biomarkers to improve the risk assessment of benzene at Superfund sites and ambient locations close to known point sources of benzene. Earlier research, based on urinary metabolites in 189 Chinese females indicated that benzene is metabolized by two pathways and that one pathway (high-affinity pathway) efficiently metabolizes benzene at low environmental exposure levels. This year, the research team has finalized analyses of metabolite levels in 732 subjects of both genders from both China and Italy. Results indicate that the high-affinity pathway is more active in females than males and is inhibited by smoking in both genders. This has important implications for calculating cancer risks from benzene exposure at low levels of exposure. Analysis of GWAS data is ongoing. With the Quantitative Biology: Biostatistics, Bioinformatics, and Computation Core, the research team has developed methods to analyze reduced representation bisulfate sequencing (RRBS) DNA methylation data, and miRNA data, separately and together with previously generated mRNA microarray data. Finally, the team has applied a new ‘omics’ assay, developed in their laboratory, to further investigate benzene metabolism. The assay called ‘adductomics’ detects all products (adducts) of reactions between reactive chemicals in the blood and human serum albumin (HSA), a prominent protein. Using archived serum from only 10 benzene-exposed workers and 10 controls from China, the team detected highly significant differences in adduct levels, suggesting that benzene produces a signature of adducts that may be useful in evaluating effects of exposure in epidemiologic studies. These results provided preliminary data for their Superfund renewal application.

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