The doxorubicin cardioprotective agent dexrazoxane (ICRF-187) induces endopolyploidy in rat neonatal myocytes through inhibition of DNA topoisomerase II.
Dexrazoxane (ICRF-187), which is clinically used to reduce doxorubicin-induced cardiotoxicity, is also a potent catalytic inhibitor of DNA topoisomerase II. In this study we showed that dexrazoxane inhibited the division of neonatal rat ventricular myocytes in culture, and resulted in nuclear multilobulation (demonstrated by three-dimensional reconstruction of confocal images) and marked increases in nuclear size and DNA ploidy levels (as shown by flow cytometry). It was concluded that dexrazoxane interfered with cell division in cardiac myocytes by virtue of its ability to inhibit topoisomerase II.
Hasinoff
Brian B
BB
Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada. B_Hasinoff@UManitoba.CA
Takeda
Kazuyo
K
Ferrans
Victor J
VJ
Yu
Zu-Xi
ZX
D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects*; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism*; D011123:Polyploidy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011929:Razoxane / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D059005:Topoisomerase II Inhibitors; D011929:Razoxane; D004317:Doxorubicin; D004247:DNA