Mitotic disturbance by carbaryl and the metabolite 1-naphthol may involve kinase-mediated phosphorylation of 1-naphthol to the protein phosphatase inhibitor 1-naphthylphosphate.
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.
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
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Renglin
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Olsson
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Wachtmeister
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Onfelt
D000818:Animals; D012721:Carbaryl / Q000378:metabolism / Q000494:pharmacology*; D006224:Cricetinae; D016195:G2 Phase / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D009281:Naphthalenes / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D009284:Naphthols / Q000378:metabolism / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D009281:Naphthalenes; D009284:Naphthols; D009943:Organophosphorus Compounds; D011506:Proteins; D014316:Tritium; C029350:1-naphthol; C014694:naphthyl phosphate; D010749:Phosphoprotein Phosphatases; C028405:2-naphthol; D012721:Carbaryl; D013936:Thymidine