Genotoxicity Assessment of Drinking Water Disinfection Byproducts by DNA Damage and Repair Pathway Profiling Analysis

Abstract

Genotoxicity is considered a major concern for drinking water disinfection byproducts (DBPs). Of over 700 DBPs identified to date, only a small number has been assessed with limited information for DBP genotoxicity mechanism(s). In this study, we evaluated genotoxicity of 20 regulated and unregulated DBPs applying a quantitative toxicogenomics approach. We used GFP-fused yeast strains that examine protein expression profiling of 38 proteins indicative of all known DNA damage and repair pathways. The toxicogenomics assay detected genotoxicity potential of these DBPs that is consistent with conventional genotoxicity assays end points. Furthermore, the high-resolution, real-time pathway activation and protein expression profiling, in combination with clustering analysis, revealed molecular level details in the genotoxicity mechanisms among different DBPs and enabled classification of DBPs based on their distinct DNA damage effects and repair mechanisms. Oxidative DNA damage and base alkylation were confirmed to be the main molecular mechanisms of DBP genotoxicity. Initial exploration of QSAR modeling using moleular genotoxicity end points (PELI) suggested that genotoxicity of DBPs in this study was correlated with topological and quantum chemical descriptors. This study presents a toxicogenomics-based assay for fast and efficient mechanistic genotoxicity screening and assessment of a large number of DBPs. The results help to fill in the knowledge gap in the understanding of the molecular mechanisms of DBP genotoxicity.

Mutagenicity, genotoxicity and oxidative stress induced by pesticide industry wastewater using bacterial and plant bioassays

“…With the fast pace in the development and era of modern mechanization the problem of pollution, specifically water pollution has been increased alarmingly in numerous developing countries including India [[11], [12], [13]]. A lot of toxicants in the environment act by damaging of DNA and therefore causing mutations [[14], [15], [16]]. Genotoxicity evaluation of industrial effluents on surface water indicates the presence of mixtures comprise of various toxic substances that may stance risk of hazard and carcinogenicity [17,18].…”

Machine Learning-based Biomarkers Identification and Validation from Toxicogenomics - Bridging to Regulatory Relevant Phenotypic Endpoints

“…The details of the proteomics assay, when using GFP-tagged yeast cells, were described in the Supporting Information (Text S1) and also in our previous reports. 2,49,51…”

“…[17][18][19][20][21] Establishment of a quantitative AOP framework through integration of computational modeling with in-vitro assays would require identification and selection of relevant biomarkers from appropriate bioassays that link to risk assessment pathways and phenotypic impacts. 18,21,66 Current toxicomics approach still mostly rely on large number of redundant markers without pre-selection or ranking; 3,51,67 therefore, selection of relevant biomarkers with minimal redundancy would reduce the number of markers to be monitored and reduce the cost, time, and complexity of the toxicity risk monitoring. The method developed in this study will help to fill in the knowledge gap in phenotypic anchoring and predictive toxicology, and contribute to the progress in the implementation of tox 21 vision for environmental and health applications.…”

Chronic exposure to dichloroacetamide induces biochemical and histopathological changes in the gills of zebrafish

“…To date, over 700 DBPs were identified in the drinking water, Investigators divided them into carbonaceous disinfection by‐products (C‐DBPs) and nitrogenous disinfection by‐products (N‐DBPs) based on their precursor . The occurrence of N‐DBPs in drinking water has gained attention because these compounds are significantly more genotoxic and cytotoxic than the currently regulated C‐DBPs, such as trihalomethanes (THMs) and haloacetic acids (HAAs) . Haloacetamides (HAcAms), as one of the emerging class of N‐DBPs, has attracted notable attention due to frequent occurrence in reclaimed water and drinking water .…”