Selectivity of methyl mercury effects on cytoskeleton and mitotic progression in cultured cells

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 PtK 2 cells by immunofluorescence. At 0.5 μ m MeHg the number of microtubules was reduced. After 1.0 or 2.0 μ m 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.