Mutagenesis, Vol. 15, No. 1, 17-24,
January 2000
© 2000 UK Environmental Mutagen Society/Oxford University Press
Trichlorfon induces spindle disturbances in V79 cells and aneuploidy in male mouse germ cells
1 Institute of Mammalian Genetics and 2 Institute of Radiation Biology, GSF-National Research Centre for Environment and Health, Ingolstaedter Landstrasse, D-85764 Neuherberg, Germany and 3 Department of Toxicology, Medical College, Qingdao University, Qingdao 266021, People's Republic of China
In order to assess the effects of trichlorfon on cell division and on aneuploidy induction, we conducted an in vitro assay for spindle disturbances using V79 cells and an in vivo assay for aneuploidy induction in meiosis of male mice using multicolour fluorescence in situ hybridization (FISH) with epididymal sperm. In the in vitro assay, the chemical caused a concentration-dependent increase in the incidence of initial and full c-mitoses in the dose range 40–120 µg/ml trichlorfon. The mitotic index (MI) was decreased between 40 and 100 µg/ml trichlorfon, whereas at 120 µg/ml the MI was back to the control level, coinciding with the dramatic increase in c-mitoses. The results confirm that trichlorfon is a potent spindle poison in V79 cells. In the in vivo multicolour FISH assay, administration of trichlorfon to male mice at single doses of 200, 300 and 405 mg/kg caused a dose-dependent increase of the frequencies of disomic sperm (0.068, 0.074 and 0.134%, respectively) compared with the corresponding controls (0.046, 0.042 and 0.056%, respectively). The prevalence of X-X-8 and Y-Y-8 sperm suggests that trichlorfon affected chromosome segregation predominantly during the second meiotic division. Diploid sperm were not induced by trichlorfon treatment, indicating that no meiotic block occurred. It is concluded that trichlorfon is a potent spindle poison in V79 cells and induces aneuploidy in mouse spermatocytes during meiosis.
* To whom correspondence should be addressed. Tel: +49 89 3187 2302; Fax: +49 89 3187 2210; Email:adler{at}gsf.de
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