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PLoS One. 2011;6(8):e24205. doi: 10.1371/journal.pone.0024205. Epub 2011 Aug 30.

Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast.

Author information

  • 1Department of Nutritional Science and Toxicology, University of California, Berkeley, California, United States of America.

Abstract

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.

PMID:
21912624
[PubMed - indexed for MEDLINE]
PMCID:
PMC3166172
Free PMC Article

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