Genotoxicity Assessment of Haloacetaldehyde Disinfection Byproducts via a Simplified Yeast-Based Toxicogenomics Assay

Haloacetaldehydes (HALs) represent the third-largest category of disinfection byproducts (DBPs) in drinking water in terms of weight. As a subset of unregulated DBPs, only a few HALs have undergone assessment, yielding limited information regarding their genotoxicity mechanisms. Herein, we developed a simplified yeast-based toxicogenomics assay to evaluate the genotoxicity of five specific HALs. This assay recorded the protein expression profiles of eight Saccharomyces cerevisiae strains fused with green fluorescent protein, including all known DNA damage and repair pathways. High-resolution real-time pathway activation data and protein expression profiles in conjunction with clustering analysis revealed that the five HALs induced various DNA damage and repair pathways. Among these, chloroacetaldehyde and trichloroacetaldehyde were found to be positively associated with genotoxicity, while dichloroacetaldehyde, bromoacetaldehyde, and tribromoacetaldehyde displayed negative associations. The protein effect level index, which are molecular end points derived from a toxicogenomics assay, exhibited a statistically significant positive correlation with the results of traditional genotoxicity assays, such as the comet assay (r_p = 0.830 and p < 0.001) and SOS/umu assay (r_p = 0.786 and p = 0.004). This yeast-based toxicogenomics assay, which employs a minimal set of gene biomarkers, can be used for mechanistic genotoxicity screening and assessment of HALs and other chemical compounds. These results contribute to bridging the knowledge gap regarding the molecular mechanisms underlying the genotoxicity of HALs and enable the categorization of HALs based on their distinct DNA damage and repair mechanisms.