Toxicity profiles and solvent–toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure

Abstract

To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound-induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent-toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short- (1 day) and long-term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l(-1) ) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long-term exposure set-up, a concentration of 500 µl l(-1) DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l(-1) DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l(-1) DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l(-1) in this organism. In the second part of our study, we propose a statistical approach to account for solvent-toxicant interactions and discuss full-scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea.

Planarian brain regeneration as a model system for developmental neurotoxicology

“…; Stevens et al. ). The pLMV method is similar to methods used for quantifying rodent behaviors; see for example Yamin et al.…”

Stem cell proliferation patterns as an alternative for in vivo prediction and discrimination of carcinogenic compounds

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“…Exposures were performed in 6-well plates (4 ml/well). To exclude intrinsic effects of DMSO on cell proliferation, the DMSO vehicle concentration never exceeded 0.05% and interaction effects between the test compound and DMSO were investigated using a two-way ANOVA17.…”

“…The process of regeneration potentially influences the organism’s cellular response to toxic exposures, with massive cell proliferation being a prerequisite for both regeneration and carcinogenesis15161718. (2) Their experimentally accessible stem cells enable in vivo studies of carcinogen-induced responses of pluripotent, adult stem cells within an entire animal.…”

Hydrogen peroxide as regeneration-initiation signal that activates pERK to trigger planarian regeneration

“…Because of its hydrophobic character, DPI was prepared in 0.01% dimethylsulfoxide (DMSO, Sigma Aldrich, 471267). In all experiments concerning DPI exposure, a DMSO-exposed control group was added to take into account the possible effects of DMSO since relatively high concentrations can have neurotoxic effects and influence cell proliferation in S. mediterranea 52 .…”