A comprehensive analysis of metabolomics and transcriptomics reveals new biomarkers and mechanistic insights on DEHP exposures in MCF-7 cells.

Abstract:

:Di-(2-ethylhexyl) phthalate (DEHP) is one of the most important environmental pollutants and affects multiple pathways upon human exposure. DEHP could induce MCF-7 cell proliferation at a very low dose; however, the possible linkage between DEHP and the cell proliferation effect is still unclear. Here, we carried out a comprehensive metabolome and transcriptome analysis to depict the possible molecular mechanisms of the effect of DEHP exposure on MCF-7 proliferation. In this paper, MCF-7 cells treated with DEHP at a dose of 1 μM for 48 h were selected for metabolome and transcriptome analysis. Untargeted and targeted metabolomics identified 8 differential metabolites, including amino acids, purine, pyrimidine and nucleotides. The metabolite changes were associated with 9 metabolic pathways. Disorders in riboflavin, histidine, beta-alanine metabolism, and nitrogen metabolism caused by DEHP exposure are important concerns for MCF-7 proliferation. Moreover, a transcriptomics study of the MCF-7 cells found a total of 500 differentially expressed genes (DEGs). KEGG enrichment analyses showed that pathways in cancer had stronger responses. The results of integrated analysis of the interactions between the DEGs and metabolites revealed significant changes in the purine metabolism pathway, which will shed light on the mechanism of MCF-7 cell proliferation after DEHP exposure. Overall, this study depicts the possible contribution of DEHP exposure to MCF-7 cell proliferation and highlights the power of omics platforms to deepen the mechanistic understanding of toxicity caused by endocrine disrupting chemicals.

journal_name

Chemosphere

journal_title

Chemosphere

authors

Lu YS,Yao GX,Wang XL,Liu JX,Yu J,Qiu J,Li Y,Qian YZ,Xu YY

doi

10.1016/j.chemosphere.2020.126865

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

126865

eissn

0045-6535

issn

1879-1298

pii

S0045-6535(20)31058-4

journal_volume

255

pub_type

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