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Updated: Aug 12, 2026
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Selectivity of methyl mercury effects on cytoskeleton and mitotic progression in cultured cells
1Cellular and Reproductive Toxicology, ICI Americas, Inc., Farmington, Connecticut 06032.
Abstract:
Methyl mercury (MeHg) disrupts microtubules, but effects on other cytoskeleton components are not well studied. Dose-effect relationships were used to determine the selectivity of MeHg effects on vimentin intermediate filaments, actin microfilaments, and microtubules. These were examined in PtK2 cells by immunofluorescence. At 0.5 microM MeHg the number of microtubules was reduced. After 1.0 or 2.0 microM MeHg, microtubules in most cells were disassembled except for a few "stable" microtubules. No effects on vimentin or actin filaments were observed except as secondary effects at concentrations of MeHg that caused extensive microtubule disassembly. Antimitotic effects of MeHg are well known. An assay based on fluid pinocytosis was used here to study kinetics of mitotic progression. HeLa cells were arrested at prometaphase with a lengthening of subsequent stages of mitosis. Progression from prophase to prometaphase was not affected. MeHg treatment also increased the number of micronucleated and multinucleated cells. Drugs specific for actin cause similar effects by blocking cytokinesis but the selective action of MeHg on microtubules argues against this mechanism. Data from both interphase and mitotic cultured cells indicate that MeHg acts selectively on microtubules. It further supports the hypothesis that the mechanism of damage of MeHg is related to its antimicrotubule activity.
Insights
Methyl mercury (MeHg) selectively damages microtubules, impacting cell division. This study confirms MeHg
Area of Science:
- Cell Biology
- Toxicology
- Neuroscience
Background:
- Methylmercury (MeHg) is a potent neurotoxin.
- MeHg is known to disrupt microtubules, but its effects on other cytoskeletal components are less understood.
Purpose of the Study:
- To investigate the selectivity of MeHg on microtubules, actin microfilaments, and vimentin intermediate filaments.
- To elucidate the mechanism underlying MeHg's antimitotic effects.
Main Methods:
- Dose-response experiments using immunofluorescence in PtK2 cells.
- Assay based on fluid pinocytosis to study mitotic progression in HeLa cells.
- Analysis of micronucleation and multinucleation.
Main Results:
- MeHg significantly reduced microtubule numbers at 0.5 microM and caused disassembly at higher concentrations.
- Vimentin and actin filaments remained unaffected except as secondary consequences of microtubule disruption.
- MeHg treatment prolonged mitotic stages and increased micronucleated/multinucleated cells, suggesting impaired cytokinesis.
Conclusions:
- MeHg exhibits selective toxicity towards microtubules.
- The antimitotic activity of MeHg is primarily mediated by its interaction with microtubules, not actin.
- Findings support the hypothesis that MeHg's toxicity is linked to its antimicrotubule activity.
