Methylmercury, but not inorganic mercury, causes abnormality of centrosome integrity (multiple foci of gamma-tubulin), multipolar spindles and multinucleated cells without microtubule disruption in cultured Chinese hamster V79 cells.
Abnormalities of centrosome integrity and spindle organization in the cultured Chinese hamster fibroblast cell line V79 exposed to methylmercury (MeHgCl) and inorganic mercury (Hg(2+)) were investigated in conjunction with inductions of mitotic arrest and multinucleated cells. The centrosome integrity and spindle organization were investigated by immunofluorescence of centrosome proteins, gamma-tubulin, and beta-tubulin, respectively. MeHgCl at subtoxic concentrations caused an increase in mitotic index 6 h after exposure. Ameboid cells with multiple pseudopodia were also induced and chromosomes were distributed even in the pseudopodia. After the increase in mitotic index caused by MeHgCl, multinucleated cells with multiple micronuclei appeared. MeHgCl caused abnormality of centrosome integrity (multiple foci of gamma-tubulin) colocalized with aberrant spindles in a concentration-dependent manner, while it did not cause disruption of centrosome integrity and microtubule organization in interphase cells. In addition, MeHgCl led to the appearance of monoastral cells with a one-dot signal of gamma-tubulin. By contrast, Hg(2+) did not cause any of the changes induced by MeHgCl. Thus, MeHgCl caused centrosome abnormality and the related changes without microtubule disruption, suggesting that the mitotic centrosome is a critical target for the cytotoxic effects of MeHgCl.
Ochi
Takafumi
T
Department of Toxicology and Environmental Health, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan. tkfmochi@pharm.teikyo-u.ac.jp
D000818:Animals; D002478:Cells, Cultured; D018385:Centrosome / Q000187:drug effects* / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D007150:Immunohistochemistry; D008297:Male; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D008767:Methylmercury Compounds; D014404:Tubulin; D008628:Mercury; C004925:methylmercuric chloride