Chapter 11: Application of Transcriptomics in Exposed Human Populations: Benzene as an Example

Benzene is an industrial chemical and widespread environmental contaminant that causes acute myeloid leukemia and probably other hematological malignancies. Human exposure to benzene below the current occupational exposure limit of 1 ppm causes hematotoxicity and other effects. Transcriptomics can identify biomarkers of exposure and early effect, particularly at low levels of exposure, which can be used to inform risk assessment. The human transcriptome is complex, with multiple transcript types and additional variation such as alternative splicing, all aspects of which can potentially be dysregulated by environmental exposures. Here, we provide an overview of our recent transcriptomic approaches and findings in a population of Chinese workers occupationally exposed to benzene. We describe our application of microarrays, RNA-sequencing, and NanoString as well as future approaches such as the L1000/S1500 platforms. Using microarrays, we have identified a signature of benzene exposure and shown that leukemia-related gene and pathway expression is altered at very low levels of exposure. Using RNA-sequencing, we have identified alternative splicing as a potential mechanism of benzene toxicity and have explored the identification of fusion transcripts and non-human sequences. We discuss our findings in the context of platform choice, study design considerations and application in risk assessment.