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肾脏转录组学揭示了氨基甲酸乙酯在小鼠中的致癌机制。

Renal Transcriptomics Reveals the Carcinogenic Mechanism of Ethyl Carbamate in Musalais.

作者信息

Wang Weihua, Han ZhanJiang, Guo Dongqi, Xiang Yanju

机构信息

College of Life Science, Tarim University, Xinjiang Uygur Autonomous Region, Alaer City, 843300, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Feb 25;14:1401-1416. doi: 10.2147/OTT.S282125. eCollection 2021.

DOI:10.2147/OTT.S282125
PMID:33658803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7920598/
Abstract

INTRODUCTION

Musalais is a traditional fermented wine produced in southern Xinjiang (a province of China) and is protected as a form of national intangible cultural heritage. However, ethyl carbamate (EC), which is naturally produced during the fermentation process, has been shown to induce carcinogenesis and was classified as a group 2A carcinogen by The World Health Organization's International Agency for Research on Cancer.

METHODS

In this work, rats were treated with musalais containing EC at varying contents (0.1, 1, or 10 mg/kg). To evaluate the toxicity of EC in musalais, the liver and kidney of the rats were subjected to transcriptomics sequencing. Differentially expressed genes (DEGs) between treated and untreated rats were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed on these genes to investigate the biological functions affected by EC in musalais.

RESULTS

The results demonstrated that high EC content in musalais is possibly involved in the regulation of cytochrome P450 metabolism, chemical carcinogenesis, metabolism of xenobiotics by cytochrome P450, Wnt signaling, and p53 signaling by targeting Mgst1, Gstp1, Gsta5, Gsta1, Adh1, Gsta2, and Ccnd1, thereby inducing cancer.

CONCLUSION

The present work predicted the potential carcinogenic mechanism of high EC content in musalais, providing a reference for its safety evaluation.

摘要

引言

穆萨莱斯是中国新疆南部生产的一种传统发酵葡萄酒，被列为国家级非物质文化遗产。然而，在发酵过程中自然产生的氨基甲酸乙酯（EC）已被证明具有致癌性，被世界卫生组织国际癌症研究机构列为2A类致癌物。

方法

在本研究中，用不同含量（0.1、1或10mg/kg）的含EC穆萨莱斯处理大鼠。为了评估穆萨莱斯中EC的毒性，对大鼠的肝脏和肾脏进行转录组测序。鉴定处理组和未处理组大鼠之间的差异表达基因（DEG），并对这些基因进行基因本体论和京都基因与基因组百科全书富集分析，以研究穆萨莱斯中EC影响的生物学功能。

结果

结果表明，穆萨莱斯中高含量的EC可能通过靶向Mgst1、Gstp1、Gsta5、Gsta1、Adh1、Gsta2和Ccnd1参与细胞色素P450代谢、化学致癌作用、细胞色素P450对外源化学物的代谢、Wnt信号传导和p53信号传导的调控，从而诱发癌症。

结论

本研究预测了穆萨莱斯中高含量EC的潜在致癌机制。为其安全性评价提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/24ae71337496/OTT-14-1401-g0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/24ae71337496/OTT-14-1401-g0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/3a9ce0722b0a/OTT-14-1401-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/a9c4addfeb07/OTT-14-1401-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/a7c23b8d827f/OTT-14-1401-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/3ac38bd7fb4b/OTT-14-1401-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/85ef5b7ce3e1/OTT-14-1401-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69de/7920598/24ae71337496/OTT-14-1401-g0009.jpg

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