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Identification of Key Toxic Substances Considering Metabolic Activation: A Combination of Transcriptome and Nontarget Analysis.
Chou, Liben; Zhang, Shaoqing; Luo, Wenrui; Zhu, Wenxuan; Guo, Jing; Tu, Keng; Tan, Haoyue; Wang, Chang; Wei, Si; Yu, Hongxia; Zhang, Xiaowei; Shi, Wei.
Afiliación
  • Chou L; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Zhang S; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Luo W; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Zhu W; Department of Mathematics, Statistics, and Computer Science, Macalester College, Saint Paul, Minnesota 55105, United States.
  • Guo J; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Tu K; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Tan H; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Wang C; Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, Institute of Environment and Health, Jianghan University, Wuhan 430056, China.
  • Wei S; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Yu H; Jiangsu Province Ecology and Environment Protection Key Laboratory of Chemical Safety and Health Risk, Nanjing 210023, China.
  • Zhang X; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
  • Shi W; Jiangsu Province Ecology and Environment Protection Key Laboratory of Chemical Safety and Health Risk, Nanjing 210023, China.
Environ Sci Technol ; 58(33): 14831-14842, 2024 Aug 20.
Article en En | MEDLINE | ID: mdl-39120612
ABSTRACT
There have been numerous studies using effect-directed analysis (EDA) to identify key toxic substances present in source and drinking water, but none of these studies have considered the effects of metabolic activation. This study developed a comprehensive method including a pretreatment process based on an in vitro metabolic activation system, a comprehensive biological effect evaluation based on concentration-dependent transcriptome (CDT), and a chemical feature identification based on nontarget chemical analysis (NTA), to evaluate the changes in the toxic effects and differences in the chemical composition after metabolism. Models for matching metabolites and precursors as well as data-driven identification methods were further constructed to identify toxic metabolites and key toxic precursor substances in drinking water samples from the Yangtze River. After metabolism, the metabolic samples showed a general trend of reduced toxicity in terms of overall biological potency (mean 3.2-fold). However, metabolic activation led to an increase in some types of toxic effects, including pathways such as excision repair, mismatch repair, protein processing in endoplasmic reticulum, nucleotide excision repair, and DNA replication. Meanwhile, metabolic samples showed a decrease (17.8%) in the number of peaks and average peak area after metabolism, while overall polarity, hydrophilicity, and average molecular weight increased slightly (10.3%). Based on the models for matching of metabolites and precursors and the data-driven identification methods, 32 chemicals were efficiently identified as key toxic substances as main contributors to explain the different transcriptome biological effects such as cellular component, development, and DNA damage related, including 15 industrial compounds, 7 PPCPs, 6 pesticides, and 4 natural products. This study avoids the process of structure elucidation of toxic metabolites and can trace them directly to the precursors based on MS spectra, providing a new idea for the identification of key toxic pollutants of metabolites.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Contaminantes Químicos del Agua / Transcriptoma Idioma: En Revista: Environ Sci Technol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Contaminantes Químicos del Agua / Transcriptoma Idioma: En Revista: Environ Sci Technol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos