A trivalent dimethylarsenic compound, dimethylarsine iodide, induces cellular transformation, aneuploidy, centrosome abnormality and multipolar spindle formation in Syrian hamster embryo cells.
The abilities of dimethylarsine iodide (DMI), a model compound of trivalent dimethylarsenicals, to induce cellular transformation, aneuploidy, centrosome abnormality, and multipolar spindle formations were investigated using the Syrian hamster embryo (SHE) cell model. Cellular growth was decreased in a concentration-dependent manner by treatment with DMI at concentrations over 0.1 microM. Treatment with DMI at concentrations from 0.1 to 1.0 microM induced morphological transformation in SHE cells. The transforming activity of DMI, determined by the frequency of morphologically transformed colonies, was approximately 30 times higher than that induced by treatment with the same concentration of sodium arsenite. Flow cytometry suggested an increase in the aneuploid population caused by DMI, as shown by the appearance of hypo-2N, hypo-4N and hypo-8N. DMI also caused abnormal staining of gamma-tubulin, indicating loss of centrosome integrity and a resultant induction of multipolar spindles in mitotic cells. Mitotic cells with centrosomes that coalesced partly at the cell periphery, not the cell center, were detected as early changes that resulted in multipolar spindles. These findings indicate that DMI has transforming activity in SHE cells. Moreover, the results suggest the importance of centrosome abnormalities as a causal change of DMI-induced aneuploidy.
Ochi
Takafumi
T
Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan. tkfmochi@pharm.teikyo-u.ac.jp
Suzuki
Toshihide
T
Barrett
J Carl
JC
Tsutsui
Takeki
T
D000782:Aneuploidy; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D018385:Centrosome / Q000187:drug effects*; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008647:Mesocricetus; D008870:Microtubules / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D008941:Spindle Apparatus / Q000187:drug effects*
D001152:Arsenicals; C062856:dimethylarsine; D004247:DNA