Citation:

Ekman, D., Y. Yue, Z. Huajun, T. Collette, P. Bradley, J. Mosley, AND Q. Teng. Assessing the Bioactivity of Surface Waters with Metabolomics Using Multiple Cell Lines. SETAC North America 44th Annual Meeting, Louisville, KY, November 12 - 16, 2023.

Impact/Purpose:

Development of cell-based NAMs for environmental monitoring

Description:

We have used cell culture-based metabolomics to investigate the biological impacts of complex mixtures of contaminants in water samples collected from eight streams across the United States and Puerto Rico. These streams were part of a larger nationwide study and were chosen based on their differing land-use characteristics and contaminant profiles. Two types of human cell lines (liver cell culture HepG2 and brain cell culture LN229) and one fish cell line (zebrafish liver cell culture ZFL) were exposed for 48 hours to water samples from each of the eight streams. We applied high resolution liquid chromatography-mass spectrometry (HR LC-MS) to measure changes in endogenous polar metabolite profiles of the cells (relative to controls). We then used these changes to compare the overall impact of each contaminant mixture on the different cell lines as well as the primary biological pathways that were affected. These analyses revealed differing sensitivities and differing changes in metabolite profiles for the three cell lines following exposure to these contaminated environmental samples. ZFL generally exhibited the greatest sensitivity, while HepG2 exhibited the most robust resistance to environmental stressors, possibly due to the cell line’s innate growth characteristics and detoxification capability. Finally, we identified covariances between metabolite changes and contaminant concentrations across all sites and cell lines. This revealed generally strong covariances between human cell lines and pharmaceutical contaminants. Pesticides covaried most strongly with hepatic-based cell lines (HepG2 and ZFL) regardless of species, while neuroactive contaminants covaried particularly well with the human brain cell line (LN229). These results both demonstrate the diverse and complementary strengths of these cell lines for investigating complex mixtures of contaminants and recommend continued development of new approach methodologies for environmental effects-based monitoring. The contents of this abstract neither constitute nor reflect US EPA policy.

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