Presence of topoisomerases and their functions in spermatogenic cells
This thesis examined the expression of topoisomerases I and II in rat and Xenopus spermatogenesis and the functions of topo II in Xenopus spermatogenic cells. Topoisomerase I and II protein and activity levels were highest in tetraploid spermatocytes, and decreased as cells progressed through spermatogenesis, in both species. Sperm were negative. The only exception was that there may be a subset of elongate spermatid (steps 11-13) in rat that contained high levels of topo I and II, perhaps to relieve torsional stress during the nucleohistone/protamine transition. The enzymes were mostly nuclear, and topo II$\alpha$ was the predominant form in the cells. Xenopus germ cells appeared to contain a germline specific topo I isoform (165 kDa). Using two different topo-reactive drugs (VM-26 and ACLA) that work via different mechanisms, it was determined that topo II functions in chromosome condensation and segregation. Pachytene spermatocytes may undergo an apoptotic cell death when treated with VM-26, while some fraction of pachytene cells cultured with ACLA assume an interphase-like morphology and are unable to progress to metaphase. This suggests that there is a cell-cycle checkpoint at pachytene. The meiotic divisions were inhibited most strongly by the drugs, while spermatid development was relatively unaffected by the drugs. Both drugs caused the induction of micronuclei, at doses which are comparable to those used in chemotherapeutic regimens. Thus, topo II drugs may cause the induction of mutations which may be passed on to subsequent generations.
Morse-Gaudio, Michele, "Presence of topoisomerases and their functions in spermatogenic cells" (1996). ETD Collection for Fordham University. AAI9628348.