Effects of the DNA topoisomerase II inhibitor merbarone in male mouse meiotic divisions in vivo: Cell cycle arrest and induction of aneuploidy
✍ Scribed by Morko Kallio; Jaana Lähdetie
- Book ID
- 102655944
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 559 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
In order to clarify possible risks of aneuploidy induc-highest level of MN induction (5.8 MN/1000 spertion in germ cells by cancer chemotherapy we stud-matids, P õ 0.001) was observed in animals inied effects of a non complex-stabilizing DNA topo-jected 48 hours before the harvest, corresponding isomerase II (topo II) inhibitor merbarone in male to the treatment of diplotene-diakinesis spermatomouse meiotic divisions in vivo. Two cytogenetic cytes. Most of the induced MN (80%) contained approaches were used: (1) C-banding on meiotic kinetochore signals, indicating that they resulted chromosome preparations and (2) analysis of sper-from detachment of a whole bivalent or chromomatid micronuclei (MN) combined with immunocy-some from the meiotic spindle. The high frequency tochemical staining of kinetochore proteins using of MN with two kinetochore signals at opposite sides CREST serum. For comparison, another topo II inhib-(33%) most likely denotes lagging of whole bivalents itor, VP-16, known to form cleavable complexes, during MI. Inhibition of cell proliferation was deterwas studied. The microdissection technique of mined by scoring cells arrested at different phases of mouse seminiferous tubules enabled us to carefully MI and MII. All groups of treated animals showed a examine effects at specific phases of meiosis. Merb-clear increase in the frequency of arrested divisions arone injections increased percentages of polyploid compared to controls (P õ 0.001). Thus, merbarone and hypoploid metaphase II spermatocytes at time was shown to severely damage normal meiotic prointervals corresponding to the treatment of the first cesses.