Transcriptomic and metabolomic approaches to investigate molecular responses of human cell lines exposed to flame retardants

Zhang, Jinkang (2015). Transcriptomic and metabolomic approaches to investigate molecular responses of human cell lines exposed to flame retardants. University of Birmingham. Ph.D.

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Abstract

With intensive and global usage, flame retardants (FRs) have played critical roles in the prevention of fires for decades. However, there are increasing concerns about the potential adverse effects of these chemicals due to the well documented environmental and human exposures to FRs. To date, relatively little is known about the molecular mechanisms of the potential toxic effects of human exposure to FRs. In this study, microarray-based transcriptomics and direct injection mass spectrometry based metabolomics were employed to investigate the molecular responses of human lung cancer cells (A549) and human hepatoma cells (HepG2/C3A) exposed to a range of sub-lethal concentrations of hexabromocyclododecane (HBCD), tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) and a mixture of FRs at equivalent concentrations to those found in typical household dust. Combined with the quantification of FRs levels in cells after exposure, this work using the non-targeted capabilities of multi-omics approaches has revealed that at the concentrations investigated, and which are relevant to human exposures, significant molecular perturbations are not induced by exposure to the FRs under study. The results from this thesis are beneficial for both understanding the potential mechanisms of effects of human exposure to FRs and for future risk assessment of these chemicals.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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