TY  - JOUR
A1  - Stopper, Helga
A1  - Kirchner, S.
A1  - Schiffmann, D.
A1  - Poot, M.
T1  - Cell cycle disturbance in relation to micronucleus formation induced by the carcinogenic estrogen diethylstilbestrol
N2  - In addition to its tumor-promoting activity in honnone-receptive tissue, the carcinogenic estrogen diethylstilbestrol (DES) has been found to induce cell transformation, aneuploidy and micronucleus formation in mammalian cells. The majority of these micronuclei contained whole chromosomes and were fonned during mitosis. Here a possible relationship between a disturbance in cell cycle progression and micronucleus fonnation is investigated by exposing Syrian hamster embryo (SHE) cells to DES. Continuous bromodeoxyuridine labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry was employed for analysis of cell cycle transit and related to the time course of micronucleus formation. Treatment of SHE cells with DES resulted in delayed and impaired cell activation (exit from the GO/G 1 phase), impaired S-phase transit and, mainly, G2-phase traverse. Cells forming micronuclei, on the other hand, were predominantly in G2 phase during DES treatment. These results suggest that impairment of Sand G2 transit may involve a process ultimately leading to micronucleus formation.
KW  - Toxikologie
KW  - Flow cytometry
KW  - Micronucleus formation
KW  - Diethylstilbestrol
KW  - Hoechst 33258 dye
KW  - Bromodeoxyuridine labeling
KW  - continuous
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82250
ER  - 
TY  - JOUR
A1  - Janevski, J.
A1  - Choh, V.
A1  - Stopper, Helga
A1  - Schiffmann, D.
A1  - De Boni, U.
T1  - Diethylstilbestrol alters the morphology and calcium levels of growth cones of PC12 cells in vitro
N2  - Diethylstilbestrol (DES) is a synthetic estrogen with carcinogenic properties. DES is known to alter cytoskeletal components, including the organization of actin stress fibres in C6 rat glioma cells. ln a test of the hypothesis that DES disrupts actin Filaments of growth cones in neuron-like cells, DES-induced changes in filopodial lengths were quantified in rat pheochromocytoma (PC12) cells in vitro. DES significantly altered growth cone morphology, with collapse of growth cone filopodia and neurite retraction invariably occurring at a concentration of 10 MikroM. At 5 MikroM DES, transient reductions in total filopodiallengths occurred. At DES concentrations of 0.1 nM and 1 nM, reductions in total filopodiallengths occurred in a fraction of growth cones. Evidence exists which shows that growth cone activity and morphology are intimately linked to Ieveis of intracellular, free calcium and that DES increases such levels. Measurements of free intracellular calcium levels by fluorescence microscopy, at times concurrent with the DES-induced reduction in total filopodial lengths, showed that calcium levels were indeed significantly increased by 10 MirkoM DES. Labelling of filamentaus actin (f-actin) with FITC-phalloidin showed that the f-actin distribution in growth cones exposed to DES could not be differentiated from the distribution found in spontaneously retracting growth cones. Tagether with evidence which showed that growth cone motility was not affected, the results are taken to indicate that DES, rather than acting directly on the cytoskeleton, exerts its effects indirectly, by a calcium-induced destabilization of actin filaments in the growth cone.
KW  - Calcium
KW  - Zellskelett
KW  - Wachstumskonus
KW  - Diethylstilbestrol
KW  - Diethylstilbestrol
KW  - rat pheochromocytoma cells
KW  - growth cone
KW  - cytoskeleton
KW  - calcium
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86858
ER  -