An in vitro attempt at precision toxicology reveals the involvement of DNA methylation alteration in ochratoxin A-induced G0/G1 phase arrest
Autor: | Boyang Zhang, Liye Zhu, Yaqi Dai, Hongyu Li, Kunlun Huang, Yunbo Luo, Wentao Xu |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: | |
Zdroj: | Epigenetics, Vol 15, Iss 1-2, Pp 199-214 (2020) |
Druh dokumentu: | article |
ISSN: | 1559-2294 1559-2308 15592294 |
DOI: | 10.1080/15592294.2019.1644878 |
Popis: | Precision toxicology evaluates the toxicity of certain substances by isolating a small group of cells with a typical phenotype of interest followed by a single cell sequencing-based analysis. In this in vitro attempt, ochratoxin A (OTA), a typical mycotoxin and food contaminant, is found to induce G0/G1 phase cell cycle arrest in human renal proximal tubular HKC cells at a concentration of 20 μM after a 24h-treatment. A small number of G0/G1 phase HKC cells are evaluated in both the presence and absence of OTA. These cells are sorted with a flow cytometer and subjected to mRNA and DNA methylation sequencing using Smart-Seq2 and single-cell reduced-representation bisulfite sequencing (scRRBS) technology, respectively. Integrated analysis of the transcriptome and methylome profiles reveals that OTA causes abnormal expression of the essential genes that regulate G1/S phase transition, act as signal transductors in G1 DNA damage checkpoints, and associate with the anaphase-promoting complex/cyclosome. The alteration of their DNA methylation status is a significant underlying epigenetic mechanism. Furthermore, Notch signaling and Ras/MAPK/CREB pathways are found to be suppressed by OTA. This attempt at precision toxicology paves the way for a deeper understanding of OTA toxicity and provides an innovative strategy to researchers in the toxicology and pharmacology field. |
Databáze: | Directory of Open Access Journals |
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