9717170 |
Renglin A, Olsson A, Wachtmeister CA, Onfelt A: Mitotic disturbance by carbaryl and the metabolite 1-naphthol may involve kinase-mediated phosphorylation of 1-naphthol to the protein phosphatase inhibitor 1-naphthylphosphate. Mutagenesis. 1998 Jul;13(4):345-52. Carbaryl causes depolymerization of spindle microtubules and apparent uncoupling of karyokinesis and cytokinesis in mitotic V79 cells. The metabolite 1-naphthol has virtually identical effects at equimolar concentrations. The closely related 2-naphthol causes similar configurations, but at a much lower frequency than 1-naphthol, showing that there are some structural requirements for these effects in mitosis. The results of the present study demonstrate that the effects of treatment are reversible; briefly (30 min) treated and thoroughly rinsed cells resume the normal appearance of cells in metaphase within 5 min, followed by anaphase approximately 15 min later. It could be demonstrated that added 1-naphthol can be converted to 1-naphthylphosphate by the cells, a recognized protein phosphatase inhibitor. With the applied method no 1-naphthylphosphate could be detected in carbaryl-treated cells, although a fraction of carbaryl was found to be converted to 1-naphthol. Carbaryl, 1-naphthol and 2-naphthol caused a decrease in protein phosphorylation of about the same magnitude. We hypothesize that 1-naphthol is a substrate for a protein kinase in mitosis and the carbaryl interferes with the same kinase. Carbaryl alone or the 1-naphthylphosphate formed may also interfere with protein phosphatase activity. |
32(0,1,1,2) |