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暴露于杀虫剂可改变体外造血组织中的基因表达和 DNA 甲基化。

Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro.

机构信息

Laboratorio de Genética y Cáncer, Instituto Nacional de Pediatría, Mexico City 04530, Mexico.

Maestría y Doctorado en Ciencia y Tecnología de Vacunas y Bioterapéuticos, Doctorado en Ciencias en Biotecnología, Laboratorio de Enfermedades Osteoarticulares e Inmunológicas, Instituto Politécnico Nacional-ENMyH, Mexico City 07738, Mexico.

出版信息

Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.

DOI:10.3390/ijms24076259
PMID:37047231
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10094043/
Abstract

The evidence supporting the biological plausibility of the association of permethrin and malathion with hematological cancer is limited and contradictory; thus, further studies are needed. This study aimed to investigate whether in vitro exposure to 0.1 μM permethrin and malathion at 0, 24, 48 and 72 h after cell culture initiation induced changes in the gene expression and DNA methylation in mononuclear cells from bone marrow and peripheral blood (BMMCs, PBMCs). Both pesticides induced several gene expression modifications in both tissues. Through gene ontology analysis, we found that permethrin deregulates ion channels in PBMCs and BMMCs and that malathion alters genes coding proteins with nucleic acid binding capacity, which was also observed in PBMCs exposed to permethrin. Additionally, we found that both insecticides deregulate genes coding proteins with chemotaxis functions, ion channels, and cytokines. Several genes deregulated in this study are potentially associated with cancer onset and development, and some of them have been reported to be deregulated in hematological cancer. We found that permethrin does not induce DNA hypermethylation but can induce hypomethylation, and that malathion generated both types of events. Our results suggest that these pesticides have the potential to modify gene expression through changes in promoter DNA methylation and potentially through other mechanisms that should be investigated.

摘要

支持拟除虫菊酯和马拉硫磷与血液系统癌症之间关联的生物学合理性的证据是有限的且相互矛盾的;因此,需要进一步研究。本研究旨在调查在细胞培养开始后 0、24、48 和 72 小时,以 0.1 μM 的浓度体外暴露于拟除虫菊酯和马拉硫磷是否会引起骨髓和外周血单核细胞(BMMCs、PBMCs)中基因表达和 DNA 甲基化的变化。这两种农药都在两种组织中诱导了一些基因表达的改变。通过基因本体论分析,我们发现拟除虫菊酯在 PBMCs 和 BMMCs 中下调离子通道,而马拉硫磷改变编码具有核酸结合能力的蛋白质的基因,在 PBMCs 中暴露于拟除虫菊酯也观察到了这种情况。此外,我们发现这两种杀虫剂都下调了编码具有趋化功能、离子通道和细胞因子的蛋白质的基因。本研究中失调的几个基因可能与癌症的发生和发展有关,其中一些基因已被报道在血液系统癌症中失调。我们发现拟除虫菊酯不会诱导 DNA 超甲基化,但可以诱导低甲基化,而马拉硫磷则产生这两种类型的事件。我们的结果表明,这些农药有可能通过改变启动子 DNA 甲基化以及可能通过其他应进一步研究的机制来改变基因表达。

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