DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro

Abstract

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.

Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

“…That may be one of reasons that numerous data coming from various research groups cannot be compared-as the models of investigation may look similar but are, as shown here, entirely different. The comprehensive data on the strong DMSO effect on the two types of untransformed cell types was published only last year [30]. We were not able to find similar data with respect to ethanol application.…”

“…Special attention in this current research was dedicated to exploring the potential effect of curcumin and the solvent, absolute ethanol, which was shown as a strong modifier of the results of the MTT assays [29]. Dimethyl sulfoxide (DMSO), a commonly used solvent for curcumin, also was recently shown to be a strong modifier of cellular epigenome and, consequentially, a transcriptome in cardiomyocytes and hepatocytes [30]. The ethanol effect was obvious in all experiments.…”

Inhibition of the Inflammasome Signaling Cascade Reduces Alcohol Consumption in Female But Not Male Mice

“…In our study, it is also important to note the limitation due to the use of DMSO as a vehicle for treatment administration. DMSO has documented effects on inflammation that may influence our target pathways (the inflammasome cascade) and downstream proinflammatory signaling (Verheijen et al, ). Additionally, we used 0.5% and 1% DMSO to optimally dilute MCC950 and VX765, respectively, and 1% DMSO was used as a common vehicle control for these groups.…”

Tivantinib, A c-Met Inhibitor in Clinical Trials, Is Susceptible to ABCG2-Mediated Drug Resistance

“…The result suggested that, within 72 h, a low dose of tivantinib was able to upregulate ABCG2 protein levels in drug resistant cells, which confirmed ABCG2 protein upregulation as a reason for increased drug resistance. It has been reported that solvent DMSO may affect gene expression or cellular process [38,39]. In Figure S1, we ruled out the possibility that DMSO treatment can upregulate ABCG2 expression, indicating that the upregulation of ABCG2 is due solely to tivantinib treatment.…”