Toxicogenomics, Maastricht University, Maastricht, Netherlands.
Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
Sci Rep. 2019 Mar 15;9(1):4641. doi: 10.1038/s41598-019-40660-0.
Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.
尽管在 20 世纪 60 年代，二甲亚砜（DMSO）的医学应用临床试验报告了其毒性，但后来 FDA 将 DMSO 归类为最安全的溶剂类别。DMSO 在许多生物医学领域得到了广泛应用，其生物学效应被忽视了。与此同时，生物医学科学朝着敏感的高通量技术和新的研究领域发展，包括表观基因组学和 microRNAs。考虑到其广泛的用途，特别是在冷冻保存和体外检测中，我们使用这些技术创新来评估 DMSO 的生物学效应。我们将 3D 心脏和肝脏微组织暴露于含有或不含有 0.1%DMSO 的培养基中，并分析了转录组、蛋白质组和 DNA 甲基化谱。在这两种组织类型中，转录组分析检测到 >2000 个差异表达基因，这些基因影响相似的生物学过程，从而表明 DMSO 在不同器官之间具有一致的作用。此外，microRNA 分析揭示了心脏 microRNAs 的大规模失调，以及肝脏微组织中虽小但仍大规模的效应。全基因组甲基化模式也显示出组织特异性。虽然肝脏微组织显示出非显著变化，但心脏微组织的结果表明，DMSO 可能破坏了 DNA 甲基化机制，导致全基因组变化。microRNAs 的极端变化和表观遗传景观的改变表明 DMSO 并非惰性物质。应重新考虑其用途，特别是在胚胎和卵母细胞的冷冻保存方面，因为它可能会影响胚胎发育。
