Effects of aflatoxin and fumonisin on gene expression of growth factors and inflammation-related genes in a human hepatocyte cell line.

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY Mutagenesis Pub Date : 2024-04-24 DOI:10.1093/mutage/geae005
Hang Wu, Ya Xu, Yun Yun Gong, John Huntriss, Michael N Routledge
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Abstract

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely distributed in maize and maized-based products, often occurring together. The implications of co-exposure to aflatoxin and fumonsin for human health are numerous, but a particular concern is the potential of FB1 to modulate AFB1 hepatotoxicity. This study evaluated the toxicity of these mycotoxins, alone or combined, in a human non-tumorigenic liver cell line, HHL-16 cells, and assessed the effects of AFB1 and FB1 on expression of genes involved in immune and growth factor pathways. The results demonstrated that in HHL-16 cells, both AFB1 and FB1 had dose-dependent and time-dependent toxicity, and the combination of them showed a synergistic toxicity in the cells. Moreover, AFB1 caused upregulation of IL6, CCL20, and BMP2, and downregulation of NDP. In combination of AFB1 with FB1, gene expression levels of IL6 and BMP2 were significantly higher compared to individual FB1 treatment, and had a tendency to be higher than individual AFB1 treatment. This study shows that FB1 may increase the hepatoxicity of AFB1 through increasing the inflammatory response and disrupting cell growth pathways.

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黄曲霉毒素和伏马菌素对人肝细胞系生长因子和炎症相关基因表达的影响
黄曲霉毒素 B1(AFB1)和伏马菌素 B1(FB1)是广泛存在于玉米和以玉米为原料的产品中的霉菌毒素,通常同时出现。同时接触黄曲霉毒素和伏马菌毒素对人体健康的影响是多方面的,但特别令人担忧的是 FB1 可能会调节 AFB1 的肝毒性。这项研究评估了这些霉菌毒素在人类非致癌肝细胞系 HHL-16 细胞中单独或混合产生的毒性,并评估了 AFB1 和 FB1 对参与免疫和生长因子途径的基因表达的影响。结果表明,在 HHL-16 细胞中,AFB1 和 FB1 都具有剂量依赖性和时间依赖性毒性,它们的组合对细胞具有协同毒性。此外,AFB1 会导致 IL6、CCL20 和 BMP2 上调,NDP 下调。在 AFB1 与 FB1 联用的情况下,IL6 和 BMP2 的基因表达水平明显高于单独使用 FB1 的情况,并且有高于单独使用 AFB1 的趋势。这项研究表明,FB1 可能会通过增加炎症反应和破坏细胞生长途径来增加 AFB1 的肝毒性。
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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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